The spring-back phenomenon: does the final position of the nipple areola complex correspond to the pre-operative markings in reduction mammoplasty?

This study investigates whether tissue recoil or patient intrinsic factors influence the final position of the nipple areola complex (NAC) after reduction mammoplasty. The age, pre-operative ptosis, BMI and weight of the tissue resected were recorded as patient intrinsic factors in 37 patients undergoing reduction mammoplasty. The “spring-back” value was defined as the distance from the sternal notch to a nipple landmark on the breast meridian with the patient sitting up, minus the same measurement repeated with the patient recumbent to eliminate the pull of gravity on the breast. Spring back was measured pre-operatively for the nipple and nipple mark then post-operative for the nipple. The difference in centimeters between the final post-operative distance from the sternal notch to the nipple and the level intended by the pre-operative nipple mark was termed the “judgment error.” The final position of the post-operative nipple and the judgment error was compared to the spring-back values and patient intrinsic factors. Pre-operative ptosis was statistically related to increasing patient BMI and mass of tissue resected per breast. Pre-operative spring-back values for the nipple increased with increasing ptosis, BMI and decreasing age. Spring-back values were greater in the lower pole of the breast than in the upper pole. The final position of the nipple was higher than the pre-operative mark in 65% of cases, lower in 8% and as marked in 27% of cases. The post-operative NAC was, on average, 0.6 cm higher than planned pre-operatively. The post-operative distance from the sternal notch to the nipple increased with increasing pre-operative ptosis, mass of breast tissue resected per breast and all three spring-back values. The difference between the level of the pre-operative mark and the final nipple position showed a weak correlation with post-operative spring-back values. The parameters of ptosis, BMI, weight of tissue resected per breast and pre-operative nipple spring back reflect body habitus and breast size. Spring-back values vary between the upper and lower pole of the breast. The final NAC position was higher than that intended at pre-operative marking in the majority of cases. The surgeon instinctively marks the nipple lower in patients with greater pre-operative ptosis and in whom a larger resection is anticipated. Judgment error did not relate to intrinsic factors nor to pre-operative spring-back values; hence, these parameters cannot be applied as predictive tools for more accurate pre-operative marking of the nipple position. This study suggests that the pre-operative nipple mark should be placed, with the patient sitting up, at least 23 cm from the sternal notch and 0.6 cm lower than the final position estimated using the inframammary crease as a landmark. An invited commentary on this paper is available at .     

Mortality in patients with diabetic neuropathic osteoarthropathy (Charcot foot).

OBJECTIVE: To determine the mortality of a population of patients diagnosed with Charcot neuropathic osteoarthropathy managed by a single specialist unit and to compare the results with a control population. METHODS: We have undertaken a retrospective analysis of all cases of Charcot foot on the comprehensive database which has been maintained at the specialist diabetic foot clinic at the City Hospital, Nottingham since 1982. Survival and the incidence of amputation (major and minor) was compared with a control population referred with uncomplicated neuropathic ulceration. Controls were individually matched for gender, age (+/-2 years), disease type, disease duration (+/-2 years) and year of referral (+/-3 years). RESULTS: Forty-seven cases (21 female, 26 male) of Charcot foot were identified, of whom 18 (38.3%) had Type 1 diabetes. Mean age and disease duration at presentation were 59.2 +/- 13.4 (sd) and 16.2 +/- 11.2 years, compared with 59.7 +/- 12.6 and 16.3 +/- 11.2 years, respectively, in the controls. Twenty-one (44.7%) of those with Charcot had died, after a mean interval of 3.7 +/- 2.8 years. This compared with 16 (34.0%) after a mean 3.1 +/- 2.7 years in the control group. Mean duration of follow-up in the survivors was 4.7 +/- 4.9 years (Charcot) and 5.3 +/- 3.9 years (controls). A total of 11 (23.4%) Charcot patients had had a major amputation on the side of the index lesion, compared with five (10.6%) controls. There was no difference between the two groups (P > 0.05, Chi-square). CONCLUSIONS: The mortality in this group of patients with Charcot foot was higher than expected. Nevertheless, there was no difference between those with Charcot and those with uncomplicated neuropathic ulceration. It is possible that it is neuropathy, rather than Charcot osteoarthropathy, which is independently associated with increased mortality in diabetes. The mechanism underlying any such association is not known. There is a need for a formal, prospective, multicentre study to investigate the life expectancy and cardiovascular risk of those with Charcot osteoarthropathy.     

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.     

Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer

Optical technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide improved point-of-care detection methods for cervical neoplasia that are sensitive, specific, and cost-effective. Our specific goals are to analyze the diagnostic potential of reflectance and fluorescence spectra, alone and in combination, to discriminate normal and precancerous cervical tissue in vivo and to identify which classification features contain significant diagnostic information. Reflectance spectra are measured at four source-detector separations and fluorescence emission spectra are measured at 16 excitation wavelengths, from 324 sites in 161 patients. These 20 spectral features are permuted in all possible combinations of one, two, and three; and classification algorithms are developed to evaluate the diagnostic performance of each combination. Algorithms based on fluorescence spectra alone yield better diagnostic performance than those based on reflectance spectra alone. The combination of fluorescence and reflectance do not significantly improve diagnostic performance compared to fluorescence alone, except in the case of discriminating high-grade precancers from columnar normal tissue. In general, fluorescence emission spectra at 330- to 360-nm and 460- to 470-nm excitation provide the best diagnostic performance for separating all pairs of tissue categories.     

Flow cytometric analysis of procalcitonin expression in human monocytes and granulocytes

Fluorescent monoclonal antibody labelling followed by a lysed whole blood method and flow cytometry was used to determine the lymphocyte subpopulations in 127 (64 males and 63 females) normal healthy individuals in the adult (age 18-59 years) Kuwaiti population. Relative percentages and absolute values of CD2+, CD3+, CD19+, CD4+, CD8+, HLADR+, CD56+, CD45RO+, and CD45RA+ cells were determined. The reference ranges were CD2+, 73-92% (0.95-2.99 x 10(9) per l), CD3+, 64-85% (0.83-2.71 x 10(9) per l), CD19+, 6-22% (0.05-0.61 x 10(9) per l), CD4+, 34-54% (0.45-1.65 x 10(9) per l), CD8+, 20-42% (0.29-1.17 x 10(9) per l), HLADR+, 4-23% (0.02-0.62 x 10(9) per l), CD56+, 4-22% (0.06-0.58 x 10(9) per l), CD45RO+, 16-53% (0.26-1.42 x 10(9) per l) and CD45RA+, 35-72% (0.34-2.05 x 10(9) per l). The mean CD4/CD8 ratio was 1.50+/-0.35. CD3+ cells were positively correlated to both CD4+ and CD8+ cells (P<0.001), and CD4+ cells showed a significant positive correlation with CD8+ cells (P<0.001).     

A duplication/paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene

X-linked deafness with stapes fixation (DFN3) is caused by mutationsin the POU3F4 gene at Xq21.1. By employing pulsed field gelelectrophoresis (PFGE) we identified a chromosomal aberrationin the DNA of a DFN3 patient who did not show alterations inthe open reading frame (ORF) of POU3F4. Southern blot analysisindicated that a DNA segment of 150 kb, located 170 kb proximalto the POU3F4 gene, was duplicated. Fluorescence in situ hybridization(FISH) analysis, PFGE, and detailed Southern analysis revealedthat this duplication is part of a more complex rearrangementincluding a paracentric inversion involving the Xq21.1 region,and presumably the Xq21.3 region. Since at least two DFN3-associatedminideletions are situated proximal to the duplicated segment,the inversion most likely disconnects the POU3F4 gene from aregulatory element which is located at a distance of at least400 kb upstream of the POU3F4 gene.     

How communication about risk and role affects women’s decisions about birth after caesarean

Objective

This study investigated how health care provider communication of risk information, and women’s role in decision-making, influenced women’s preferences for mode of birth after a previous caesarean birth.

X-linked mixed deafness (DFN3): cloning and characterization of the critical region allows the identification of novel microdeletions

We have found that the microsatellite marker AFM207zg5 (DXS995)maps to all previously described deletions which are associatedwith X-linked mixed deafness (DFN3) with or without choroideremiaand mental retardation. Employing this marker and pHU16 (DXS26)we have identified two partially overlapping yeast artificialchromosome clones which were used to construct a complete 850kb cosmid contig. Cosmids from this contig have been testedby Southern blot analysis on DNA from 16 unrelated males withX-linked deafness. Two novel microdeletions were detected inpatients which exhibit the characteristic DFN3 phenotype. Bothdeletions are completely contained within one of the known DFN3-deletions,but one of them does not overlap with two previously describeddeletions in patients with contiguous gene syndromes consistingof DFN3, chorolderemia, and mental retardation. Assuming thatonly a single gene is involved, this suggests that the DFN3gene spans a chromosomal region of at least 400 kb.     

Molecular mechanisms that set the stage for DC-T cell engagement

The unsurpassed capacity of dendritic cells (DC) to prime naive T cells is thought to depend on the formation of an immunological synapse. DC-SIGN, a C-type lectin exclusively expressed at the cell surface of DC, functions as an adhesion receptor facilitating T cell binding and priming through recognition of glycosylated ICAM-3 on naive T cells. Yet, DC-SIGN also mediates binding to pathogens such as HIV by recognizing glycosylated gp120. The scope of the present study was to investigate whether DC-SIGN upon recognition of its cellular ligand and pathogenic ligand affects DC synapse formation and activation/mobilization of other adhesion receptors such as LFA-1 to the cell contact site. Using a DC-SIGN deletion mutant, we show that DC-SIGN is a constitutively active receptor that mediates ligand binding independent of signaling through the cytoplasmic domain. Surprisingly, initial binding of gp120 to DC-SIGN did not result in increased adhesion levels of LFA-1 to its ligand ICAM-1 in both immature DC and Raji-DC-SIGN cells. However, ligand binding to DC-SIGN induced recruitment of LFA-1 to the adhesion site. Moreover, we could demonstrate that activation of LFA-1 results in DC-SIGN-LFA-1 co-clustering in the cell membrane. This triggers binding of ligands to LFA-1 that are shared with DC-SIGN, such as ICAM-3, but not of ligands that are not shared with DC-SIGN, such as ICAM-1. Thus, we propose that upon ligand binding DC-SIGN recruits LFA-1 to the contact site, resulting in the formation of DC-SIGN-LFA-1 co-clusters, in which the initial DC-SIGN-mediated interactions with ligand are transient and eventually shift to more stable LFA-1-dependent interactions.