Management of metastatic breast cancer

Systemic treatment almost certainly prolongs the median survival of women with metastatic breast cancer, and it may prolong the survival of a small number of patients substantially. Even with conventional therapy, 10% or more patients may live into the second decade after recurrence. However, the disease cannot be eradicated, and the primary goal of treatment remains palliation and improvement of the quality of life. Because of the great variability in the pattern and course of the disease from one patient to another, therapy should be selected judiciously to maximize response and minimize toxicity. In some clinical situations, such as pathologic fractures and brain metastases, local therapies alone, such as surgery or irradiation, are the treatments of choice. Patients who will respond to endocrine therapy are well defined, and all patients with the characteristics of an endocrine responder deserve a chance at palliation with this modality alone because of its limited toxicity. A number of new forms of endocrine therapy with more specific targets at estrogen and progesterone receptor sites are now in clinical trials. When used appropriately, chemotherapy significantly improves patient quality of life despite its toxicity. No drug combinations, schedules, or doses have been shown to prolong survival or provide better net palliation than classic CMF (oral cyclophosphamide with intravenous methotrexate and 5-fluorouracil) or CAF (intravenous cyclophosphamide, doxorubicin, and 5-fluorouracil). Treatment with these combinations in excess of 6 to 9 months provides only marginal additional benefits and no survival advantage. The role of high dose chemotherapy with autologous bone marrow transplantation remains a promising area of investigation, but the available survival data are entirely compatible with the possibility that this modality will eventually prove inferior to conventional therapy. Many new cytotoxic agents with unique mechanisms of action are currently under investigation, including taxol, taxotere, Topotecan, and amonafide. Taxol may be the most promising therapy now available for patients whose disease has become refractory to doxorubicin. Biologic therapies using monoclonal antibodies against a specific oncogene or its product have entered clinical trials, and novel drug delivery systems using liposomes are under evaluation.

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Resumen El tratamiento sistémico casi ciertamente prolonga la supervivencia media de las mujeres con cáncer mamario metastásico y logra prolongar la sobrevida de un muy pequeño número de pacientes en forma muy sustancial. Aún con terapia convencional, 10% o más de las pacientes sobreviven hasta la segunda década después de una recurrencia. Sin embargo, la enfermedad no puede ser erradicada y el objetivo primario del tratamiento sigue siendo paliativo para mejorar la calidad de vida. Teniendo en cuenta la gran variabilidad del patrón y de la evolución de la enfermedad entre una y otra paciente, la terapia debe ser cuidadosamente seleccionada a fin de lograr la máxima respuesta y minimizar la toxicidad. En algunas situaciones clínicas, tales como las fracturas patológicas y las metástasis cerebrales, las solas modalidades de terapia local, tales como la cirugía o la irradiación, constituyen los tratamientos de elección. Las pacientes que puedan responder a la terapia endocrina están bien definidas, y todas las pacientes con las características de ser una de las que responda al manejo endocrino merece la oportunidad de paliación con esta modalidad, en virtud de su limitada toxicidad. Variadas y nuevas formas de terapia endocrina con miras más específicas en cuanto a receptores de estrógeno y de progesterona se encuentran en ensayo. Cuando la quimioterapia es utilizada en forma apropiada, ésta mejora significativamente la calidad de vida a pesar de su toxicidad. Ninguna combinación de drogas, programas o dosificaciones ha demonstrado prolongar la sobrevida o lograr mejor paliación que el régimen clásico CMF (ciclofosfamida oral con metotrexato IV y 5-fluorouracilo). El tratamiento con estas combinaciones por más de 6–9 meses provee apenas beneficios adicionales marginales y ninguna ventaja en cuanto a sobrevida. El papel de la quimioterapia de altas dosis con trasplante autólogo de médula ósea permanece como una promisoria área de investigación, pero la información sobre supervivencia hasta ahora disponible es enteramente compatible con la posibilidad de que esta modalidad llegue a demostrar ser inferior a la terapia convencional. Muchos nuevos agentes citotóxicos con mecanismos de acción únicos están siendo investigados en la actualidad. Estos incluyen el taxol, el taxotere, el Topotecan y el amonafide. El taxol puede ser la forma más promisoria de terapia actualmente disponible para pacientes cuya enfermedad se ha hecho resistente a la doxorubicina. Las terapias biológicas usando anticuerpos monoclonales contra un oncogene específico o su producto han ingresado a los ensayos clínicos y novedosos sistemas de administración de drogas, utilizando liposomas, también se hallan en proceso de investigación.

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Résumé Le traitement par voie systémique prolonge la survie médiane des patientes ayant un cancer métastatique du sein et peut également prolonger, sans doute, la survie d'un petit nombre d'autres patientes quel que soit le dégréé de sévérité de la maladie. Même avec une thérapeutique conventionnelle, 10% ou plus des patientes peuvent espérer survivre plus de 10 ans après leur récidive. La maladie ne peut, dans ce cas cependant, être enrayée et le but de la thérapeutique restera palliatif et d'améliorer la qualité de vie. En raison de la grande variabilité du type et de l'évolutivité de la maladie d'une patiente à l'autre, chaque protocole thérapeutique se doit d'être élaboré de façon à maximaliser la réponse tout en minimisant la toxicité. Dans certaines situations cliniques, telles les fractures pathologiques ou les métastases cérébrales, les thérapeutiques locales, telles la chirurgie ou l'irradiation, sont de modalités thérapeutiques de choix. On connaît aussi une catégorie de patientes qui répondent bien au traitement hormonal, qui devraient toutes être traitées par cette modalité étant donnée le peu de toxicité. Un certain nombre de ces traitements hormonaux sont actuellement l'objet d'essais thérapeutiques. Utilisée judicieusement la chimiothérapie améliore de façon significative la qualité de vie, et ce souvent, malgré sa toxicité. Aucune combinaison de médicaments ni de régimes ou de doses ne se sont montrés plus efficaces pour prolonger la survie ou améliorer le confort mieux que la classique association CMF (cyclophosphamide per os, methotrexate et 5-Fluorouracil par voie intraveineuse) ou la CAF (cyclophosphamide, doxorubicine, 5-fluorouracil par voie intraveineuse). Un traitement par ces combinaisons pendant plus de 6–9 mois n'apporte guère d'avantages, sans prolonger la survie pour autant. Le rôle de la chimiothérapie à hautes doses combinée avec la greffe de moelle osseuse était une voie prometteuse mais pour le moment, il semble exister de preuves en faveur de son infériorìté par rapport aux traitements conventionnels. D'autres nouvelles substances cytotoxiques, faisant intervenir d'uniques mécanismes d'actions, sont actuellement en cours d'évaluation. Ces nouveaux médicaments comprennent le taxol, le taxotère, le Topotécane, et l'amonafide. Le taxol est probablement celuì qui a le plus d'intérêt, semble-t'il, e cas de résistance à la doxorubicine. Des traitements biologiques, utilisant des anticorps spécifiques dirigés contre tel on tel oncogèn ou son produit, ainsi que de nouveaux systèmes d'apport des médicaments sont également au stade d'évaluation clinique.

     

Mechanisms of connective tissue damage by crystals containing calcium

From available clinical, radiographic, and synovial fluid findings, coupled with in vivo radiolabelled crystal turnover data and in vitro experimental data, a hypothesis has been formulated relative to the pathogenesis of BCP crystal deposition diseases (Fig. 2). Synovial lining cells phagocytose BCP crystals and particulate collagens in the joint fluid. During and/or after internalization these cells are stimulated in a variety of ways: 1) protease synthesis and secretion is relentlessly stimulated, which may damage joint tissues producing clinically evident loss of collagenous tissues including cartilage, bone, and tendon, and which may release additional amounts of crystals and particulate collagens into the synovial fluid, completing a vicious cycle; 2) PGE2 production is greatly augmented; 3) DNA synthesis is stimulated as a result of increased inositol phospholipid turnover and intracellular crystal dissolution. The increased number of synovial cells also augments the total local generation of proteases and prostenoids. Mechanical factors such as trauma or joint overuse also contribute to the pathogenesis of joint destruction as discussed in the article on the clinical aspects of BCP crystal deposition.     

Practice of orthokeratology by a group of contact lens practitioners in Hong Kong

Purpose: The aim of the study was to provide information about the characteristics of three main types of orthokeratology (ortho‐k) lenses used in Hong Kong and to report on their performance based on the clinical impressions of a group of ortho‐k practitioners. Method: Twelve ortho‐k practitioners were interviewed between 1 March and 30 June 2001. Results: Most ortho‐k lenses were ordered from three manufacturers: DreimLens, Fargo and Contex. The median maximum myopia reduction reported for DreimLens, Contex and Fargo lenses were 6.25 D, 6.00 D and 4.50 D respectively. The time to reduce myopia by up to 4.00 D could be up to three weeks for Contex and DreimLens and up to four weeks for Fargo. For reduction of myopia by up to 4.00 D, the treatment usually required only one or two lenses per eye for all three types of lenses. The incidence of lens binding and lens tightening after achieving the optimal reduction was reported to be higher with the DreimLens design. Good centration, less lens binding, relatively lower incidence of complications and lens tightening after achieving the optimal reduction were reported with the Fargo lenses. Conclusions: DreimLens tended to be more effective for myopia reduction. However, some practitioners were concerned with the aggressiveness of myopia reduction using this lens design and the higher potential for ocular complications. Selection of the lens design is dependent on various factors, in particular, practitioners need to be comfortable with the design they choose and to consider the needs of their patients and the final goal of the treatment.     

Osgood-Schlatter lesion: fracture or tendinitis? Scintigraphic, CT, and MR imaging features.

To determine whether the Osgood-Schlatter lesion (OS) is produced by avulsion fracture or injury to the patellar tendon, all images obtained in 28 cases of OS in 20 patients (16 scintigrams, 34 computed tomographic [CT] scans, and 27 magnetic resonance [MR] images) were retrospectively analyzed. In 21 cases, imaging was performed before and after treatment; in 20 cases, relief from pain was complete at the time of repeat examination. In all patients (100%), abnormal size of the tendon, decreased attenuation, and increase in signal intensity were compatible with the CT and MR imaging appearance of tendinitis. Distended deep infrapatellar bursa was a frequent finding, particularly on MR studies. These abnormalities had partially disappeared at follow-up examination. An ossicle was seen in only nine of 28 cases (32%); in three of seven cases with follow-up, the ossicle remained nonunited to the tibial tuberosity on follow-up studies despite relief from symptoms. This implies that healing of fracture is not essential for relief from symptoms. These results strengthen the argument that in most cases of OS, insult to the tendon and associated soft tissues, rather than avulsion fracture, causes OS.     

Can marital selection explain the differences in health between married and divorced people? From a longitudinal study of a British birth cohort

In view of the rising divorce rates, the impact of divorce on health has an increasing importance in public health. The differentials in health between the married and the divorced may be explained by ‘marital selection’ and ‘marital protection’. Using longitudinal data from a study of the 1958 British birth cohort, factors that select people into divorce were identified from the areas of socio-economic status, health, and attractiveness, which included physical attractiveness, health-related behaviour and temperament. Evidence for both positive and adverse selection is found. The different sets of selection factors for females and males appear to be in line with gender role expectations. The health differentials between married and divorced men were weak and can be explained away by the selection factors. Having controlled for the selection effects, there were still significant associations between divorce and physical and psychological health in women. Though these unexplained differentials cannot be definitely interpreted as the consequences of marital dissolution, this interpretation remains plausible.     

The simultaneous occurrence of renal artery stenosis and an aldosteronoma in a patient with hypertension

The simultaneous occurrence of renovascular hypertension and an adrenocortical adenoma is a rare entity. The case of a 64-year-old woman who underwent an aortorenal bypass graft for renovascular hypertension requiring a multidrug antihypertensive regimen is presented. Persistently elevated blood pressures in the postoperative period prompted further workup for other causes of hypertension. Laboratory evaluation showed hyperaldosteronism and hyporeninemia despite enalapril administration. Abdominal computerized tomography (CT) revealed a left adrenal mass which, on surgical removal, was found to be a cortical adenoma. Subsequently, her antihypertensive therapy has been reduced to a single agent. Previous authors have described only four patients with malignant hypertension who had the rare clinical combination of renal artery stenosis and an aldosteronoma. This case reemphasizes the critical need for a thorough search for other surgically correctable lesions in those patients who remain severely hypertensive after the "definitive" operation.     

Identification of Aeromonas strains to the genospecies level in the clinical laboratory.

One hundred thirty-three strains of Aeromonas (human, n = 102; animal, n = 16; environmental, n = 15) previously identified to the DNA group level by molecular methods were biochemically analyzed for 58 properties. On the basis of the use of between 9 and 16 selected tests, 132 of the 133 strains (99%) could be assigned to their correct hybridization group using this biochemical scheme. The results suggest a feasible approach for identifying aeromonads to genospecies level under appropriate conditions.     

Carbon plasma immersion ion implantation of nickel-titanium shape memory alloys

Nickel-titanium (NiTi) shape memory alloys possess super-elasticity in addition to the well-known shape memory effect and are potentially suitable for orthopedic implants. However, a critical concern is the release of harmful Ni ions from the implants into the living tissues. We propose to enhance the corrosion resistance and other surface and biological properties of NiTi using carbon plasma immersion ion implantation and deposition (PIII&D). Our corrosion and simulated body fluid tests indicate that either an ion-mixed amorphous carbon coating fabricated by PIII&D or direct carbon PIII can drastically improve the corrosion resistance and block the out-diffusion of Ni from the materials. Our tribological tests show that the treated surfaces are mechanically more superior and cytotoxicity tests reveal that both sets of plasma-treated samples favor adhesion and proliferation of osteoblasts.