Persistence and resistance as complementary bacterial adaptations to antibiotics.

Bacterial persistence represents a simple of phenotypic heterogeneity, whereby a proportion of cells in an isogenic bacterial population can survive exposure to lethal stresses such as antibiotics. In contrast, genetically based antibiotic resistance allows for continued growth in the presence of antibiotics. It is unclear, however, whether resistance and persistence are complementary or alternative evolutionary adaptations to antibiotics. Here, we investigate the co-evolution of resistance and persistence across the genus Pseudomonas using comparative methods that correct for phylogenetic nonindependence. We find that strains of Pseudomonas vary extensively in both their intrinsic resistance to antibiotics (ciprofloxacin and rifampicin) and persistence following exposure to these antibiotics. Crucially, we find that persistence correlates positively to antibiotic resistance across strains. However, we find that different genes control resistance and persistence implying that they are independent traits. Specifically, we find that the number of type II toxin-antitoxin systems (TAs) in the genome of a strain is correlated to persistence, but not resistance. Our study shows that persistence and antibiotic resistance are complementary, but independent, evolutionary adaptations to stress and it highlights the key role played by TAs in the evolution of persistence.

Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient's management and therapy selection

BACKGROUND: Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored. METHODS: Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated. RESULTS: The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014). CONCLUSIONS: The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection (AU)

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18F-FDG PET-CT imaging in the neoadjuvant setting for stages II-III breast cancer: association of loco­regional SUVmax with classical prognostic factors.

AIM: Classical prognostic and predictive factors serve to predict outcome and response to neoadjuvant treatment in stage II and III breast cancer. The purpose is to determine the relation between the SUVmax of the locoregional disease with these classical prognostic factors. METHODS: A prospective study including 43 stage II and III breast cancer patients was performed. In all the patients, two 18F-FDG PET-CT studies were performed before and after neoadjuvant chemotherapy. After this treatment, surgery and adjuvant treatment were carried out. To combine the information of the locoregional disease, the SUVmax of the lesion (tumor or abnormal lymphnodes) with the highest uptake was used. SUVmax and prognostic factors were studied with the Kruskal-Wallis non-parametric test and with the Mann-Whitney U. RESULTS: A statistically significant association between elevated SUVmax value and absence of estrogen receptors (ER) expression (16 vs.. 10; P<0.019) was found. Locorregional disease with positive HER2 phenotype had a statistically significant SUVmax value greater than Luminal A (estrogen and/or progesterone positive receptors with Ki67<15%) and B (estrogen and/or progesterone positive receptors with Ki67≥to 15%) (13.4 vs. 7.9 and 8.9; P<0.022 and P<0.024, respectively). Triple negative phenotype disease had higher SUVmax than Luminal A and B (15.4; P<0.030 and P<0.038). Positive correlation between the percentage of the Ki67 Proliferation Index and SUVmax (P<0.007) was demonstrated. High grade disease had a higher SUVmax than low grade (P<0.004). CONCLUSION: Locorregional SUVmax is associated to prognostic and predictive factors and reaffirms the utility of PET-CT as a tool in the common clinical practice.

Assignment of tumor subtype by genomic testing and pathologic-based approximations: implications on patient's management and therapy selection.

BACKGROUND: Breast cancer subtypes can be identified by genomic testing or pathology-based approximations. However, these classifications are not equivalent and the clinical relevance of both classifications needs to be fully explored. METHODS: Ninety-four patients were randomized to neoadjuvant single agent doxorubicin or docetaxel. Tumor subtype was assessed by pathology-based classification and by gene expression using the PAM50 plus the claudin-low predictor (CLP). Kappa Cohen's coefficient (κ) was used to test the agreement between methods. Multivariate Cox proportional hazards analyses were used to determine the significance of each methodology in the prediction of prognosis. Likelihood ratio statistics of both classifications were evaluated. RESULTS: The agreement between pathology-based classification and PAM50 was moderate [κ = 0.551, 95 % confidence interval (95 % CI) 0.467-0.641]. Tumor subtype assessed by both classifications were prognostic for overall survival (OS) and relapse-free survival (P < 0.05). However, PAM50 + CLP provided more prognostic information, in terms of OS, than the pathology-based classification (P < 0.05). Patients with triple negative tumors as well as basal-like tumors had worse OS when first treated with doxorubicin (HR = 5.98, 95 % CI 1.25-28.67, and HR = 5.02, 95 % CI 0.96-26.38, respectively). However, claudin-low tumors did not show significant differences in OS according to neoadjuvant treatment branch. Indeed, we found that claudin-low tumors treated with pre-operative doxorubicin had significantly better OS than basal-like tumors treated with neoadjuvant doxorubicin (adjusted HR = 0.16, 95 % CI 0.04-0.69, P = 0.014). CONCLUSIONS: The assignment of tumor subtype can differ depending on the methodology, which might have implications on patient's management and therapy selection.

Correlation between response to neoadjuvant chemotherapy and survival in locally advanced breast cancer patients.

BACKGROUND: Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts long-term survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. PATIENTS AND METHODS: We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient (К) was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). RESULTS: The agreement between Miller and Payne classification and RCB classes was very high (К = 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (К = 0.52) and RCB classes and RECIST criteria (К = 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). CONCLUSIONS: The pathological assessment of tumor response might provide stronger prognostic information in LABC patients.

Prospective transGEICAM study of the impact of the 21-gene Recurrence Score assay and traditional clinicopathological factors on adjuvant clinical decision making in women with estrogen receptor-positive (ER+) node-negative breast cancer.

BACKGROUND: This study examined the impact of the Recurrence Score (RS) in Spanish breast cancer patients and explored the associations between clinicopathological markers and likelihood of change in treatment recommendations. PATIENTS AND METHODS: Enrollment was offered consecutively to eligible women with estrogen receptor-positive; human epidermal growth factor receptor 2-negative, node-negative breast cancer. Oncologists recorded treatment recommendation and confidence in it before and after knowing the patient's RS. RESULTS: Treatment recommendation changed in 32% of 107 patients enrolled: in 21% from chemohormonal (CHT) to hormonal therapy (HT) and in 11% from HT to CHT. RS was associated with the likelihood of change from HT to CHT (P < 0.001) and from CHT to HT (P < 0.001). Confidence of oncologists in treatment recommendations increased for 60% of cases. Higher tumor grade (P = 0.007) and a high proliferative index (Ki-67) (P = 0.023) were significantly associated with a greater chance of changing from HT to CHT, while positive progesterone receptor status (P = 0.002) with a greater probability of changing from CHT to HT. CONCLUSIONS: Results from the first prospective European study are consistent with published experience and use of the RS as proposed in European clinical practice guidelines and provide evidence on how Oncotype DX and clinicopathological factors are complementary and patient selection may be improved.

Glutathione S-transferase P1 c.313A > G polymorphism could be useful in the prediction of doxorubicin response in breast cancer patients.

BACKGROUND: Identification of predicting factors for anthracyclines-based chemotherapy remains a clinical challenge. Glutathione S-transferase (GSTs) enzymes detoxify chemotherapy drugs and their metabolites. Several polymorphisms in GST genes result in reduced or no activity of the enzymes. Specifically, GSTM1 and GSTT1 genes are polymorphically deleted, the polymorphism GSTP1 c.313A>G (rs1695) determines the amino acid substitution Ile105Val, where the Val-containing enzyme has reduced activity. Also, GSTA1*B allele has reduced levels of GSTA1 enzyme. Several polymorphisms in GSTs have been associated with differences in survival for cancer patients treated with chemotherapy. PATIENTS AND METHODS: We genotyped a total of five polymorphisms in GSTM1, GSTT1, GSTP1 and GSTA1 genes in 159 patients with locally advanced breast cancer, treated with single-agent doxorubicin or docetaxel (Taxotere). Gene expression microarrays were performed in 67 breast tumor samples. We correlate this data with treatment outcome. RESULTS: In multivariate analysis, patients homozygous GG for GSTP1 c.313A>G SNP had a lower risk of chemoresistance when treated with doxorubicin (odds ratio 0.106; confidence interval 0.012-0.898; P=0.040). No association was found in the docetaxel arm. Also, we found that GSTP1 expression varied significantly among breast cancer molecular subtypes. CONCLUSIONS: GSTP1 may constitute another tool contributing to individualized anthracycline-based therapy.

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer.

UNLABELLED: Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs. EXPERIMENTAL DESIGN: Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.

¿Es necesaria la técnica combinada para la detección del ganglio centinela en el cáncer de mama? / No disponible

Objetivos: Determinar si la punción con colorante mejora los resultados de la biopsia del ganglio centinela. Material y métodos: Ciento cincuenta casos de carcinoma invasor de la mama fueron sometidos a biopsia del ganglio centinela mediante técnica combinada, para determinar si la punción con colorante es rentable. Se realizó inyección subareolar indérmica de una dosis de 0,4 mCi de radioisótopico el día previo a la cirugía. Se practicó gammagrafía en todos los casos. La inyección intraparenquimatosa de 4 cc. de colorante se realizó 20 minutos antes de la cirugía, y se siguió de masaje mamario. Resultados: La tasa de migración fue 92,3% para el radioisótopo y 75% para el colorante (p = 0,01). La media de ganglios resecados fue mayor para la técnica con colorante: 2,6 vs. 1,2 (p = 0,02). No se observaron diferencias en la tasa de falsos negativos (0,2 vs. 0,4) ni en el valor predictivo negativo. La precisión diagnóstica fue mayor para el radioisótopo (90,3% vs. 75% (p = 0,001). El mismo resultado se obtuvo para el porcentaje de éxito técnico (92,3 vs. 75% (0,001)). Conclusiones: La punción con colorante no añade información a la realizada con radioisótopo. A pesar de que la técnica se debe adaptar a las necesidades del centro y a las habilidades del cirujano, una vez superada la curva de validación la técnica radioisotópica por sí misma aporta suficiente información, con menor morbilidad y coste(AU)

Objetives: To determine whether blue dye enhances sentinel node biopsy detection. Material and methods: One hundred fifty hundred consecutive cases of breast cancer were submitted to sentinel node biopsy by combined technique in order to analyze if vital blue was cost-efective. Radioisotope dose was 0,4 mCi of Tc, subareolar intradermic inyection, the day before surgery. Gammagraphy was performed in every case. Colorant was methylene blue, 4 cc administered by intraparenchimatous inyection in upper-outer quadrant 20 minutes previous to surgery, followed by breast massagge. Results: Migration rate was 92.3% for radioisotope and 75% for colorant (p = 0.01). Mean number of nodes excised was higher for colorant: 2,6 vs. 1,2 (p = 0.02). False negative rate showed no difference (0.2 vs. 0.4) nor did negative predictive value. Accuracy to staging (True neg+ true pos./total) was higher for technecium (90.3% vs. 75% (p = 0.001) and so happenned with percentage of technical success (total- no migration): 92.3% vs. 75% (0.001). Conclusions: Colorant did no add any information concerning axillary status. More nodes had to be excised, and bigger incisions were made to achieve direct visualization. Accuracy to stage the lesion and percentage of technical success were higher with radioisotope after the learning curve is achieved and blue injection can be spared(AU)

Significado pronóstico de la densidad microvascular en el cáncer de ovario: estudio de una serie de 74 casos / Prognostic value of microvascular density in ovarian cancer in a series of 74 patients

Introducción: La cuantificación de la angiogénesis, en teoría, podría ser un factor determinante del pronóstico de ciertos carcinomas, ya que determina la posibilidad de metastatizar por parte del tumor primario. Material y métodos: Se plantea un estudio retrospectivo sobre 74 pacientes con carcinoma de ovario en estadios I-IV (FIGO) y tratados en el Hospital Clínico San Carlos (Madrid) en el período 1985-1995. Se midió el índice angiogénico (determinación con anticuerpo monoclonal CD34, y cuantificación mediante un sistema digital de análisis de imagen Leika Q500IW con software propio), y se comparó el comportamiento de tumores con angiogénesis positiva y negativa en relación con los eventos de muerte y recidiva (estudio de regresión logística). El seguimiento mediano fue de 40,5 meses (rango, 3-105). Resultados: La angiogénesis es un parámetro cuantificable, y es un factor pronóstico independiente para el riesgo relativo de muerte y recidiva para todos los estadios de carcinoma de ovario (AU)

Carcinoma neuroendocrino (tumor de Merkel) de la vulva / Neuroendocrine carcinoma (Merkel's tumor) of the vulva

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Necrosis Centrolobulillar Hepática en un caso de aspiración pulmonar masiva / Hepatic centrilobar necrosis in a case of massive pulmonary aspiration

La ecopsia es una técnica postmortem que hace ecografía del cadáver y obtiene de forma dirigidla muestras para análisis histológico.Presentamos un caso de ecopsia seguido de autopsia a una paciente de 18 meses de edad que ingresa en el servicio de urgencias por insuficiencia respiratoria aguda, por aspiración alimentaria masiva, que progresa a un síndrome de distres respiratorio del adulto, insuficiencia hepática durante la semana última y fallo cardíaco antes del exitus final.La ecopsia demostró que había múltiples zonas hipoecogénicas en el 75 por ciento del lóbulo derecho hepático, casi todo el caudado y el 15 por ciento del lóbulo izquierdo. La histopatología de las punciones de estas áreas corres-pondían a necrosis centrolobulillar que no evidenció la autopsia convencional, probablemente por ser las áreas de necrosis microscópicas y multifocales. El cuadro morfológico de necrosis centrolobulillar estaría justificado por insuficiencia cardíaca secundaria a fallo respiratorio o por la presencia de tromboembolismos de pequeños vasos similares a los encontrados en el pulmón, aunque no fueron objetivados en el estudio histológico del parénquima hepático, de la ecopsia ni de la autopsia.En general, este tipo de necrosis se observa afectando de forma difusa al hígado, pero esto no ocurría en nuestro caso. Existen algunos casos de necrosis parcheada de mecanismo no totalmente aclarado.La ecografía post-mortem evidenció las zonas necróticas que concordaban con la insuficiencia hepática en vida de la paciente y ayudó a que el estudio postmortem tuviera una mejor correlación anatomoclínica (AU)

[The cost effectiveness of echography biopsy]. / Rentabilidad de la ecopsia.

Ecopsy is a postmortem technique which, by means of echography-guided puncture and/or aspiration obtains material for histological analysis. This study compared cost and time employed in 100 ecopsies and 100 classic necropsies and confirmed that cost of materials in ecopsy is 65% lower than that in necropsy. Physicians, necropsy technicians, laboratory technicians and secretary team personnel spent 33%, 54%, 19% and 32% less time than in necropsy. The clinical report of ecopsy was finished within nine days even with the brain study included.

Heterotopic gastric mucosa in the upper esophagus ("inlet patch"): a rare cause of esophageal perforation.

We report the case of a 21-yr-old woman who presented with a perforation of an upper esophageal ulcer on a patch of gastric-type mucosa. Despite surgical closure of the perforation and reinforcement with a pleuro-muscular flap the patient developed an esophageal leakage and died in the postoperative period. Heterotopic gastric mucosa in the upper esophagus is usually an asymptomatic abnormality, discovered incidentally during endoscopic studies carried out for some other reason; however, complications secondary to the inlet patch acid secreting capacity can arise, and this has to be kept in mind to elude life-threatening conditions.

Prognostic factors in invasive lobular carcinoma of the breast: a multivariate analysis. A multicentre study after seventeen years of follow-up.

BACKGROUND AND GOALS: The purpose of this study was to characterize the biologic determinants that affect the behavior of invasive lobular carcinoma of the breast. MATERIAL AND METHODS: A prospectively accrued data base containing 9,619 breast cancer cases was queried for specific pathological features. From this data base, 390 patients with invasive lobular carcinoma of the breast treated and followed at any of these three centers: San Carlos Hospital, Doce de Octubre Hospital or The Jimenez Diaz Foundation in Madrid (Spain) were reviewed and results, in terms of overall survival and disease-free survival were recorded for a long-term follow-up of 206 months (17 years). RESULTS: The parameters that showed an important statistical influence on survival were the stage at diagnosis, the tumor size and nodal status, as well as the tumor grade. Age showed a limited influence, and multicentricity, or the type of surgical procedure had no statistical impact on survival. CONCLUSIONS: Our analysis specifies the clinico-pathological features that influence the prognosis of invasive lobular carcinoma of the breast, and confirms that conservative therapy may be an appropriate treatment for this type of cancer.

Solitary plaque-like telangiectatic glomangioma.

We present a new clinicopathological variant of glomangioma. The lesion consisted of a painful solitary telangiectatic plaque on the right shoulder of a 33-year-old woman. It had been present for 3 years. Histopathology revealed ectatic vascular lumina within the dermis surrounded by glomus cells. Immunohistochemical and ultrastructural investigations confirmed the nature of the glomus cells. Acquired solitary plaque-like telangiectatic glomangioma is a new and distinctive variant of cutaneous glomus tumour.

Clear-cell atypical fibroxanthoma: an uncommon histopathologic variant of atypical fibroxanthoma.

Atypical fibroxanthoma is a superficial variant of pleomorphic malignant fibrous histiocytoma. Histopathologically, it is characterized by a dermal nodule composed of bizarre cells arranged in a haphazard-to-fascicular pattern. These cells are spindle or rounded, pleomorphic and with numerous atypical mitotic figures. Some cells appear polygonal with ample and foamy cytoplasm. We recently encountered two elderly patients with atypical fibroxanthoma on their face. Histopathologically, one of the lesions was composed, almost entirely, of clear cells, whereas in the other one aggregations of clear cells constituted a half of the neoplasm. Atypical multinucleated cells with a Touton-like appearance were present. In addition to clear cells, areas of more conventional atypical spindle cells arranged in fascicles were seen, supporting the diagnosis of atypical fibroxanthoma. PAS staining failed to demonstrate glycogen in neoplastic cells. Immunohistochemistry revealed that neoplastic cells expressed positivity for vimentin, muscle-specific actin, and alpha smooth muscle actin, whereas cytokeratin, S-100 protein, EMA, CEA, and desmin were negative. Ultrastructural studies showed that neoplastic cells contained abundant rough endoplasmic reticulum, mitochondria, and numerous lipid vacuoles within the cytoplasm. Clear-cell atypical fibroxanthoma is a rare variant of atypical fibroxanthoma that should be differentiated from other clear-cell neoplasms of the skin.

[Non-Hodgkin's lymphoma with heart disease in patients with AIDS: clinical and echocardiographic aspects]. / Linfoma no hodgkiniano con afectación cardíaca en pacientes con SIDA: aspectos clínicos y ecocardiográficos.

We report two patients with AIDS and non-Hodgkin lymphoma evolving myocardium. Clinical findings were nonspecific, but rapid progression and cardiac dysfunction developed. An echocardiogram showed restrictive pericarditis in both cases. One of them showed mitral insufficiency because of an infiltrated and trapped posterior mitral valve.

Cutaneous adult myofibroma: a vascular neoplasm.

Infantile myofibromatosis is a distinctive type of fibromatosis that usually develops during the immediate perinatal period. There are variants with solitary and multiple tumors. Lesions confined to the skin, soft tissue, and bone carry a good prognosis, showing spontaneous regression. The prognosis, however, is much less favorable when visceral lesions are present and the outcome may be fatal. Only recently it became obvious that there is an adult counterpart of infantile myofibromatosis, characterized by solitary lesions that have a predilection for involve the dermis and show no tendency to regression, although they have an entirely benign biological behavior. These lesions have been named cutaneous myofibroma or solitary myofibroma of adults. We have studied the clinical, histopathological and immunohistochemical characteristics of 53 examples of cutaneous adult myofibroma. In addition, 2 cases were examined ultrastructurally. The patients were mostly adults with ages ranging from 6-83 years. The lesions presented as solitary, usually painless nodules of variable duration on the skin, usually located on the extremities. Histopathologically, four patterns were identified: nodular or cellular type, multinodular or biphasic type, leiomyoma-like or fascicular type, and vascular type. A correlation between the histopathologic pattern and the lesional age was observed: vascular type of cutaneous adult myofibroma in early lesions, nodular and multinodular lesions in fully developed lesions, and leiomyoma-like or fascicular type in late lesions. Immunohistochemically, the spindle cells were desmin negative, but expressed immunoreactivity for vimentin, pan-smooth muscle actin, and alpha-smooth muscle actin. Ultrastructurally, neoplastic cells showed characteristics of undifferentiated mesenchymal cells with features of fibroblasts, myofibroblasts and pericytes. Primitive vascular formations were seen in the form of irregular clefts between adjoining cells. We conclude that cutaneous adult myofibroma is a little-known benign vascular neoplasm probably derived from myopericytes.

Acrolocalized acquired cutis laxa.

A 55-year-old man presented with a 14-year history of loose, redundant skin on the palmar aspects of the finger tips and toe pulps, which gave a peculiar 'chewing gum' appearance. Skin biopsies of involved areas showed a normal appearance, and only a discrete decrease in the elastic fibres could be identified with an elastic tissue stain. Ultrastructural examination, however, demonstrated marked fragmentation and degeneration of the elastic tissue. Localized cutis laxa in an acral distribution, was fully developed at presentation. He gave a history of repeated episodes of swelling and urticaria of the involved areas, which we regard as being the initial inflammatory stages of this disease process.