Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. Received 14 April and in revised form 5 July 1997     

The fine structure of the myoneural junctions in the body wall muscles in Branchiobdella pentodonta whit. (Annelida,oligochaeta)

The ultrastructure of the myoneural junctions in the body wall muscles has been studied in Branchiobdella pentodonta Whit. A single junctional type has been found. Within the terminal axon there are two types of vesicles, which differ in number, size and electron opacity. The junctional gap contains the basement membrane. The post-junctional membrane displays concave patches on which slender projections arising from the outer lamina of the sarcolemma extend into the junctional gap. These concave patches overlie a cytoplasmic lamina made up of electron dense material.     

Gonadoblastoma in Turner syndrome and Y-chromosome-derived material

The identification of Y-chromosome material is important in females with Ullrich-Turner syndrome (UTS) due to the risk of developing gonadoblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y-chromosome-derived material and the occurrence of gonadoblastoma in these patients. The aim of our study was to evaluate a large number of patients with UTS, followed before and during the pubertal age for the prevalence of Y-chromosome derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1-34 years old), diagnosed cytogenetically, was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats). The follow-up was of 2-22 years; 101 of these patients were followed during pubertal age. Y-chromosome material was found in 14 patients (8%): 12 of these were gonadectomized (2.8-25.9 years). A gonadoblastoma was detected in four patients under 16 years of age: in two, Y-material was detected only at molecular analysis (at conventional cytogenetic analysis, one was included in the 45,X group and one in the X + mar group) and one had also an immature teratoma and an endodermal sinus carcinoma. The prevalence of gonadoblastoma in our series of gonadectomized UTS patients with Y-positive material was of 33.3% (4/12). Our data suggest that the age of appearance and the possibility of malignant degeneration of gonadoblastoma can occur early in life. These patients, in particular those with 45,X or a marker chromosome may benefit from molecular screening to detect the presence of Y-chromosome material; PCR is a rapid and inexpensive technique. At the moment, laparoscopy and preventive gonadectomy performed as soon as possible remain the procedures of choice for patients with UTS, when Y-chromosome has been identified, as we are still unable to predict a future malignant evolution of gonadoblastoma.     

Noonan-like syndrome with loose anagen hair: a new syndrome?

We present three children with short stature, the same facial phenotype, macrocephaly, enlarged cerebral spinal fluid spaces, short neck with redundant skin, severe GH deficiency, mild psychomotor delay with attention deficit/hyperactivity disorder (ADHD), mild dilatation of the pulmonary root in two of them, and a unique combination of ectodermal abnormalities. Their appearance, not completely typical of Noonan syndrome, the behavioral phenotype, GH deficiency, darkly pigmented and hairless skin, and the unusual aspect of the hair, defined as loose anagen hair syndrome did not fit any known condition. We postulate that these children may represent a distinct, previously unreported syndrome that we would name "Noonan-like syndrome with loose anagen hair".     

Effect of the synthetic retinoid fenretinide on circulating free prostate-specific antigen, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 levels in men with superficial bladder cancer.

PURPOSE: Fenretinide (4-HPR) is a synthetic retinoid that has shown a preventive activity in prostate cancer animal models. EXPERIMENTAL DESIGN: We measured the changes in total and free prostate-specific antigen (PSA) and its association with insulin-like growth factor I (IGF-I) and IGFBP-3 levels after 1 year of treatment in 24 subjects given 4-HPR and 24 control subjects enrolled in a randomized bladder cancer prevention trial. RESULTS: No significant effect of 4-HPR was observed on total and free fraction of PSA levels. The median percentage [95 confidence interval (95% CI)] change for % free PSA and total PSA in the 4-HPR and the control group were, respectively, 7.6 (95% CI, -4.0 to 69.3) versus 5.1 (95% CI, -21.4 to 59.8) and -7.8 (95% CI, -18.2 to 52.5) versus -12.3 (95% CI, -44.6 to 9.6). However, in patients ages <60 years, there was a trend to an increase of total free PSA and % free PSA after treatment with 4-HPR that was different from a trend to a decrease in the control group (P = 0.002 and 0.052, respectively). The interaction between age and treatment was statistically significant on free PSA (P = 0.001). A similar pattern was noted with smoking status (P = 0.011 for the interaction on free PSA). No association was observed between PSA levels and IGF-I or IGFBP-3 levels. CONCLUSIONS: We conclude that 4-HPR has no significant effect on circulating PSA, but it increases significantly free PSA levels in subjects younger than 60 years and in nonsmokers. These effects might support an activity in prostate cancer prevention but further studies are required.     

Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C

Background/Aims: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, being a putative steatogenic factor, may promote liver fibrosis progression in patients with chronic hepatitis C. This study aimed to verify the role of recipient MTHFR polymorphism in favouring graft fibrosis progression in patients with recurrent HCV after orthotopic liver transplantation (OLT). Methods: We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method. Results: Recipients carrying the TT genotype had more frequently, 1‐year post‐OLT, homocysteine serum levels >23 μmol/L (P<0.05), serum triglycerides >180 mg/dL (P<0.02) and de novo diabetes mellitus (P<0.05) but not a higher frequency of graft steatosis. Time‐to‐event analysis in reaching an Ishak staging score >2 was performed by stratifying the recipients as follows: (a) patients with donor age ≤45 years, (b) patients with donor age >45 and C/^* genotype, and (c) patients with donor age >45 years and TT genotype. A significant linear trend was observed, with increasing frequencies as follows: (a) 8/37, (b) 10/19 and (c) 6/7 (P=0.0005). Conclusion: The MTHFR C677T polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C, in conjunction with donor age, but not via steatosis promotion.