A cautionary case: osteoporotic femur fracture after robotic-assisted total knee arthroplasty.

Osteoporosis is a disease of low bone mass which leads to an increased risk of fracture. The prevalence of osteoporosis is greatest amongst postmenopausal women who also form a large portion of patients with osteoarthritis presenting for total knee arthroplasty. We present a case of a 77-year-old female with knee osteoarthritis and osteoporosis on denosumab who underwent robotic-assisted total knee arthroplasty. Postoperatively, she suffered an atraumatic midshaft femur fracture at the pin site associated with the use of intraoperative robotic technology. This is a unique complication related to the use of robotics which requires additional skeletal fixation versus standard arthroplasty surgical technique. We recommend caution and further study regarding the use of robotics in total knee arthroplasty in the setting of osteoporosis and denosumab use.

[Real-life WAKE study in narcolepsy patients with cataplexy treated with pitolisant and unresponsive to previous treatments]. / Estudio WAKE de vida real en pacientes con narcolepsia con cataplejía tratados con pitolisant no respondedores a tratamientos previos.

INTRODUCTION: Type 1 narcolepsy is a disabling disease that requires continuous treatment, which is not always effective. Pitolisant is a new drug with a different mechanism of action that offers a new treatment option. The objective of the study was to analyse the effectiveness and safety of pitolisant in patients with type 1 narcolepsy that did not respond to or tolerate previous standard treatments. PATIENTS AND METHODS: Real-life multicentre descriptive observational study that included patients diagnosed with type 1 narcolepsy who did not respond to or tolerate previous treatments and started treatment with pitolisant. The study evaluated three different moments: the start of treatment, the stabilization of treatment with pitolisant and the three months after. RESULTS: In 32 patients included (mean age, 44 years; 37.5% women) the mean of the Epworth Sleepiness Scale was reduced from 17.1 to 13.5; 47.8% of the patients improved from their cataplexy; 65% of the patients improved their clinical global impression at the physician's and at the patient's discretion and the mean number of medications consumed was reduced from 2.0 to 1.4. The most frequent adverse effect was insomnia in 43.8% of patients. Of the 32 patients, 23 continued with the treatment during the 3-month follow-up period. CONCLUSIONS: In patients with type I narcolepsy who do not respond to or do not tolerate the available treatments, pitolisant can improve their clinical situation and reduce their medication consumption. Studies with a higher level of evidence are needed to confirm these results.

TITLE: Estudio WAKE de vida real en pacientes con narcolepsia con cataplejía tratados con pitolisant no respondedores a tratamientos previos.Introducción. La narcolepsia de tipo 1 es una enfermedad incapacitante que requiere tratamiento continuo, que no siempre es eficaz. El pitolisant es un nuevo fármaco con un mecanismo de acción diferente que ofrece una nueva opción de tratamiento. El objetivo del estudio fue analizar la efectividad y la seguridad del pitolisant en pacientes con narcolepsia de tipo 1 que no hubieran respondido o tolerado previamente los tratamientos habituales. Pacientes y métodos. Estudio observacional descriptivo multicéntrico de vida real que incluyó a pacientes diagnosticados de narcolepsia de tipo 1 no respondedores a tratamientos previos que iniciaron tratamiento con pitolisant. El estudio evaluó tres momentos: el inicio del tratamiento, la estabilización del tratamiento con pitolisant y los tres meses posteriores. Resultados. En 32 pacientes incluidos (media de edad, 44 años; 37,5% de mujeres), la media de la escala de somnolencia de Epworth se redujo de 17,1 a 13,5; un 47,8% de los pacientes mejoró subjetivamente de su cataplejía; un 65% de los pacientes mejoró su impresión clínica global a criterio médico y a criterio del paciente; y se redujo la media de medicamentos consumidos de 2,0 a 1,4. El efecto adverso más frecuente fue el insomnio, en un 43,8% de los pacientes. De los 32 pacientes, 23 mantuvieron el tratamiento durante los tres meses de seguimiento. Conclusiones. En pacientes con narcolepsia de tipo 1 que no responden a o no toleran los tratamientos disponibles, el pitolisant puede mejorar su situación clínica y reducir su consumo de medicamentos. Son necesarios estudios de mayor nivel de evidencia para confirmar estos resultados.

An RCT on the effects of topical CGP on surgical wound appearance and residual scarring in bilateral total-knee arthroplasty patients.

OBJECTIVE: To test the hypothesis that topically applied calcium glycerophosphate (CGP) would improve the appearance of the wound following bilateral knee replacement. METHOD: Healthy patients, aged 45-75 years, scheduled for bilateral total-knee replacement surgery were recruited into the study. One knee was randomly assigned to the treatment group, while the contralateral knee was designated the control (standard care). Subjects were instructed to apply a preparation of 10% CGP in an aqueous lotion to the treated knee once daily for 42 days, starting at the third postoperative day. Functional sealing and cosmetic appearance of the incision were evaluated by two surgeons by direct examination of the patient and then by two experienced assessors from photographs. The investigators qualitatively scored the intensity and extent of erythema along the incision and over the entire knee, the appearance of visible oedema along the incision and over the knee, and the overall clinical impression of wound healing. All four assessors were blinded to the subjects' allocation and the latter two assessors to the initial investigators' assessments. Subjects were also followed up for an additional 46 weeks, giving a total study duration of 12 months. RESULTS: Twenty patients completed the study. Statistical analysis showed that both the area and intensity of erythema along the incision were significantly reduced in the treated vs untreated knee over the entire study period. The analysis further showed that treatment significantly reduced oedema, both along the incision and across the entire knee. The differences were most marked at the seventh postoperative day and diminished with time. No adverse effects were observed for any patient, in either treated or untreated knees. CONCLUSION: These data demonstrate that postoperative application of 10% CGP could improve the appearance of the wound following total knee arthroplasty.

Quantitative bone SPECT analysis of mandibular condyles in an asymptomatic population: an approach to normal reference values.

Bone scintigraphy is an extremely valuable technique in diagnosis and treatment planning for patients with condylar hyperplasia (CH). The main objective of this study was to develop an approach to determine normal activity values in the mandibular condyles, adjusted to age and sex, through quantitative analysis of bone single-photon emission computed tomography (SPECT) on a condyle-by-condyle basis and to compare these values with those of a control group comprising patients with confirmed CH. Technetium 99 m-methylene diphosphonate (99mTc-MDP) SPECT studies of the mandibular condyles were performed in patients with no mandibular pathology for quantitative analysis. Regions of interest were drawn on slices representing the upper, middle, and inferior thirds of each condyle and on the summation of transaxial slices representing the whole condyle (three-dimensional approach). The clivus was used for internal validation and the condyle to clivus ratios were calculated. These ratios were compared between 'normal' and 'diseased' condyles. A total 144 condyles in normal patients and 25 in confirmed CH patients were analysed. Differences between the ratios were evaluated through the coefficient of variation. In normal patients, the ratios to the clivus on the summed condyle image showed the lowest variability: range 0.3-1.28 (median 0.74). The quantile regression model showed significant differences with respect to sex, but not to age. The Mann-Whitney test showed significant differences in the ratios to clivus between normal and diseased condyles (P<0.0001).

Insights into toxicology, safety pharmacology, and drug dependence testing: The performance and predictive values of nonclinical tests.

The pre-marketing testing of drugs and chemicals is now a paradigm of contribution to the safeguard of public health. As pointed out by the ICH concept paper E14/S7B, there is a need for science-based frameworks that allow a better design, conduction, and interpretation of nonclinical and toxicity tests, particularly, in order for those assays to influence nonclinical and clinical evaluations and decisions better. Critical issues related to the performance and predictive values of nonclinical testing were highlighted and discussed in this article, specifically, to help pharmacologists, toxicologists, and regulators in the evaluation of the reliability of such tests, and basing the prospective decisions on the true predictivity of selected screening tests. This review addressed two common mistakes in drug and chemical testing, namely, (a) the assumption of either sensitivity or specificity as automatically "predictive," and (b) the reporting of the predictive values disregarding a truly representative prevalence. This review also discussed a statistical basis to apply for (industry standpoint) or grant (regulatory standpoint) authorization for the waiving of selected nonclinical tests. Furthermore, this review can be guiding for those who are entering into the field of drug and chemical testing. Through application, investigation, and enhancement of the conceptual framework discussed in this review, nonclinical testing is expected to provide a higher contribution to drug and chemical development, regulatory science, and public health.

In vitro anti-proliferative effect and in vivo antitumor action of daphnetin in different tumor cells.

ANTECEDENTES: Los efectos antiinflamatorios de la dafnetina (7,8-dihidroxicumarina) han sido bien documentados, pero su potencial como agente anticanceroso es controversial y no se ha explorado suficientemente. MATERIAL Y MÉTODOS: En este trabajo se evalúa el efecto antiproliferativo in vitro de la dafnetina en tres líneas celulares mediante ensayos de MTT, así como su efecto antitumoral in vivo en cuatro diferentes tipos de tumores en ratones. RESULTADOS: Con una correlación entre los resultados in vitro e in vivo, los tipos de células probadas tienen diferente sensibilidad al compuesto. Las siguientes líneas celulares están ordenadas de acuerdo con la potencia antiproliferativa in vitro de la dafnetina: células de melanoma B16 (IC50 = 54 ± 2.8 µM) > células de adenocarcinoma de mama MXT (IC50 = 74 ± 6.4 µM) > células de carcinoma de colon C26 (IC50 = 108 ± 7.3 µM). In vivo, la dosis antitumoral óptima de dafnetina fue de 40 mg/kg, y las magnitudes de inhibición fueron las siguientes: tumor B16 (48%) > tumor MXT (40%) > tumor fibrosarcoma S180 (30%) > tumor C26 (20%). CONCLUSIÓN: Los resultados indican que la dafnetina podría tener un impacto como adyuvante para mejorar la efectividad de la quimioterapia convencional.

BACKGROUND: The anti-inflammatory effects of daphnetin (7,8-dihidroxicoumarin) have been well-documented, but the potential of daphnetin as an anticancer agent is controversial and remains insufficiently explored. MATERIAL AND METHODS: In this work, we evaluated the in vitro anti-proliferative effect of daphnetin in three cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, as well as its in vivo antitumor effect in four different types of mouse tumor. RESULTS: With a correlation between in vitro and in vivo results, the tested cell types have different sensitivity to the compound. The following cell lines are arranged according to the in vitro anti-proliferative potency of daphnetin: B16 melanoma cells (inhibitory concentrations 50 [IC50] = 54 ± 2.8 µM) > mitoxantrone (MXT) breast adenocarcinoma cells (IC50 = 74 ± 6.4 µM) > C26 colon carcinoma cells (IC50 = 108 ± 7.3 µM). In vivo, the optimal antitumor dose of daphnetin was 40 mg/kg and the magnitudes of inhibition were the following: B16 tumor (48%) > MXT tumor (40%) > S180 fibrosarcoma tumor (30%) > C26 tumor (20%). CONCLUSION: Our results indicate that daphnetin might have an impact as adjuvant to improve the effectiveness of conventional chemotherapy.

Phase I enzyme induction in Girardinichthys viviparus, an endangered goodeid fish, exposed to water from native localities enriched with polychlorinated biphenyls.

The present study examines the induction of mixed-function oxidase (MFO) enzymes, including CYP content CYP1A (EROD) activity and alcohol dehydrogenase activity (ADH), in an endemic Mexican fish species, the black-fin goodeid Girardinichthys viviparus, exposed to the water of two localities, Lake Texcoco (LTX) and Lake Zumpango, and to the same matrices enriched in polychlorinated biphenyls (PCBs) to simulate the potential toxic effects of sublethal increases in these xenobiotics. Fishes of both sexes born in the laboratory were exposed for 1, 2, 4, 8, and 16 days. Water from the two types of localities of the black-fin goodeid contains MFO inducers. Of the two, the most contaminated is LTX water, which also contains PCBs. EROD activity was higher in all treatments with female compared with male fish. This suggests greater metabolic compromise in female fish as a response to damage caused by these xenobiotics. In this species, CYP induction displayed two patterns that were not always concurrent with higher CYP1A activity. In the enriched matrix system, biotransformation processes were notably altered. Increased ADH may indicate that this enzyme is involved in the biotransformation of PCBs and their metabolites, particularly in male fish, and provides at least a part of reductive power required by the MFO enzymes; however, specific studies are needed to clarify this point.

Estrogenic effects of polychlorinated biphenyls and relation to cytochrome P4501A activity in the endangered goodeid fish Ameca splendens.

The present study examines the relationships between cytochrome P4501A (CYP1A) activity and vitellogenin (VTG) induction in Ameca splendens elicited by a polychlorinated biphenyl (PCB) mixture. Ethoxyresorufin-O-deethylase (EROD) activity, mRNA levels of VTG, and VTG induction were evaluated in male and female fish exposed for 1, 2, 4, 8, and 16 d to a commercial PCB mixture. Polychlorinated biphenyls induced higher EROD in both sexes and this induction was higher in females than in males. Maximum EROD and VTG induction occurred on day 1 in females, while in males these maxima occurred on days 8 and 16. A correlation between EROD and VTG induction was found only in males (p<0.001), and VTG induction was also higher in males than in females (p<0.01). Exposure to PCBs elicited increases in VTG expression and induction over time in males, while in females these decreased at the end of the exposure period. Deficiencies in the feedback mechanisms of male A. splendens exposed in the wild to xenoestrogens such as PCBs have probably contributed to alter the sex ratio of wild populations of this species.

Characteristics of Liver Transplantation in Argentina: A Multicenter Study.

INTRODUCTION: There is a lack of information regarding outcomes after liver transplant in Latin America. OBJECTIVES: This study sought to describe outcomes after liver transplant in adult patients from Argentina. METHODS: We performed an ambispective cohort study of adult patients transplanted between June 2010 and October 2012 in 6 centers from Argentina. Only patients who survived after the first 48 hours postransplantation were included. Pretransplantation and posttransplantation data were collected. RESULTS: A total of 200 patients were included in the study. Median age at time of transplant was 50 (interquartile range [IQR] 26 to 54) years. In total, 173 (86%) patients had cirrhosis, and the most frequent etiology in these patients was hepatitis C (32%). A total of 35 (17%) patients were transplanted with hepatocellular carcinoma. In patients with cirrhosis, the median Model for End-Stage Liver Disease (MELD) score at time of liver transplant was 25 (IQR 19 to 30). Median time on the waiting list for elective patients was 101 (IQR 27 to 295) days, and 3 (IQR 2 to 4) days for urgent patients. Almost 40% of the patients were readmitted during the first 6 months after liver transplant. Acute rejection occurred in 27% of the patients. Biliary and vascular complications were reported in 39 (19%) and 19 (9%) patients, respectively. Renal failure, diabetes, and dyslipidemia were present in 40 (26%), 87 (57%), and 77 (50%) at 2 years, respectively. CONCLUSIONS: We believe the information contained in this article might be of value for reviewing current practices and developing local policies.

Reciprocal Recurrent Selection Compared to within-Strain Selection for Increasing Rate of Egg Lay of Tribolium under Optimal and Stress Conditions.

A replicated comparison of reciprocal recurrent selection (rrs) based on crossbred performance and within strain-selection (wss) based on purebred performance was made in three diverse environments over ten generations for the improvement of a heterotic trait, 4-day virgin egg lay of Tribolium castaneum. A selection intensity of 20% based on performance in either an optimum (33 degrees ), a mild stress (38 degrees ), or a severe stress (28 degrees ) environment was applied uniformly. Periodically, the performance of each population was measured in all three environments to provide both direct and correlated responses.-Heritability of egg lay in the base population ranged from 0.36 +/- 0.03 in optimum to 0.26 +/- 0.03 in severe stress. Estimates of dominance effects assumed significant proportions in severe stress only. Genetic correlations for egg lay in diverse environments were large and positive (.6 to.8).-Only in severe stress did the rrs response significantly exceed that for wss. Quadratic adjustments fitted to response curves revealed that small initial genetic gains under rrs were followed by significantly increasing rates of gain in late generations of selection. The reverse was true for wss. This and evidence from realized heritabilities and genetic correlations suggested that rrs had utilized both additive and dominance effects, but wss response was limited to additive effects.-These results agree with selection theory in demonstrating that purebred selection is more efficient than crossbred selection in utilizing additive gene effects. The latter method has merit when non-additive effects assume significant proportions, and this is the more probable case for severe stress conditions.

Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin.

Coumarin in vivo has antitumor activity in various types of cancer. In vitro, coumarin and 7-hydroxycoumarin, its major biotransformation product in humans, inhibit the proliferation of several human tumor cell lines. The molecular mechanisms of these effects are unknown. To gain information about these mechanisms, we studied the effects of coumarin and 7-hydroxycoumarin in the human lung adenocarcinoma cell line A-427 on the inhibition of: (i) cell proliferation; (ii) cell cycle progression; and (iii) expression of cyclins D1, E and A. The inhibitory concentrations 50 (IC(50)) of both compounds were estimated by cytostatic assays of tetrazolium (MTT) reduction. The effects on cell cycle progression were assayed with propidium iodide and BrdU using DNA histograms and multiparametric flow cytometry. The percentages of cells expressing cyclins D1, E, and A were estimated by means of bivariate flow cytometry using propidium iodide, and FITC-conjugated monoclonal antibodies for each cyclin. The IC(50) (+/-S.E.M. n=3) of 7-hydroxycoumarin and coumarin at 72 h exposure, were 100+/-4.8 and 257+/-8.8 microg/ml, respectively. 7-Hydroxycoumarin at the concentration of 160 microg/ml (1 mM), inhibited the G(1)/S transition of the cell cycle, an action consistent with the cytostatic effect. No significant decreases of cyclins E and A were observed. In contrast, cyclin D1 significantly decreased, which appears to indicate an action of 7-hydroxycoumarin in early events of phase G(1). However, messenger RNA of cyclin D1, assayed by RT-PCR, did not change. This suggests a posttranscriptional effect. The effects of coumarin were not significant. Cyclin D1 is overexpressed in many types of cancer, and its inhibition has been proposed as a pharmacological and therapeutic target for novel antitumor agents. Knowledge of the decrease of cyclin D1 by 7-hydroxycoumarin may lead to its use in cancer therapy, as well as to the development of more active compounds.

Hepatic chemoinfusion of 5-FU in metastasis of gastrointestinal cancer and advanced primary hepatocellular carcinoma.

From 1 January 1983 to 1 January 1988, 38 patients were treated for hepatic cancer in the HEINZ-KALK-Hospital. Thirty-one of these had liver metastases due to gastrointestinal cancer and seven had advanced primary hepatocellular cancer. In all patients more than 50% of the liver volume was involved with the tumour or the metastases. Eleven patients with liver metastases of gastrointestinal cancer (excepting colorectal cancer) were treated by intra-arterial hepatic bolus infusion of 750-1000 mg 5-fluorouracil (5-FU) by selective catheterisation of the hepatic or superior mesenteric artery after puncture of the right or left femoral artery. The median survival was 13.4 months. In seven patients with advanced primary hepatocellular carcinoma the same therapeutic regime was used. The median survival was 10 months. In the 21 patients with disseminated metastases of previously resected colorectal cancer a catheter was inserted into the gastro-duodenal artery and connected to a subcutaneously placed port. Brief infusions of 750-1000 mg 5-FU were administered for 14 days with a day interruption and thereafter 2 month interruption. There were few side effects and 80% of the patients continued to work or carry on a normal life. The median survival was 14.4 months. Based on this experience we consider hepatic chemoinfusion with 5-FU in gastrointestinal cancer and advanced primary hepatocellular carcinoma is capable of improving quality of life and possibly expectancy.

Cytostatic activity of coumarin metabolites and derivatives in the B16-F10 murine melanoma cell line.

Coumarin has antitumour effects in vivo and cytostatic effects in vitro. Its half-life in humans is short (1-1.5 h) and the monohydroxylated biotransformation products have significantly longer half-lives. One or several of these products may thus be responsible for the antitumoral effects. We have assayed the in vitro cytostatic activity of five monohydroxylated coumarins (3-, 4-, 6-, 7- and 8-monohydroxycoumarin), their acetates and methyl-ethers. Murine melanoma cells (cell line B16-F10) and murine fibroblasts (B82) were exposed to the test compounds at concentrations between 10 and 160 microg/ml. The cytostatic effects were estimated by reduction of the tetrazolium dye MTT. In the melanoma cells, some of the compounds inhibited growth after exposure for 1 day. In contrast, coumarin inhibited growth to a smaller extent, and only after exposure for 3 days. The most active compounds (3-acetoxycoumarin, 4-methoxycoumarin and 6-hydroxycoumarin), as well as coumarin, were also assayed in murine fibroblasts. The cytostatic effects of 4-methoxycoumarin and 6-hydroxycoumarin were less pronounced in fibroblasts than in melanoma cells. Our observations suggest that these compounds may have a greater therapeutic margin.

Primary polyarteritis nodosa presenting as acute symmetric quadriplegia.

We report a case of peripheral neuropathy presenting as acute symmetric areflexic quadriplegia in the setting of a well-defined clinical, histopathologic, and angiographic diagnosis of classic polyarteritis nodosa. While it is usually easy to recognize the typical clinical presentation of necrotizing angiopathy-induced peripheral neuropathy as a mononeuritis multiplex or a distal polyneuropathy in association with a collagen vascular disease, clinicians must be equally sensitive to a number of more challenging possibilities. Acute quadriplegia similar to that seen in Guillain-Barré syndrome can be secondary to primary classic polyarteritis nodosa and the former may be the chief or even the sole manifestation of the latter.

Primary cementless total hip arthroplasty in octogenarians. Two to eleven-year follow-up.

BACKGROUND: Cementless total hip arthroplasty is an accepted alternative to total hip arthroplasty with cement in younger patients, but it remains controversial for elderly patients. The purpose of this study was to evaluate the clinical and radiographic outcomes of cementless total hip arthroplasty with use of a proximally coated stem in patients who were at least eighty years of age at the time of the operation. METHODS: One hundred and twenty-three cementless total hip replacements were performed for the treatment of osteoarthritis in 114 patients between the ages of eighty and eighty-nine years. Seven patients (eight hips) died within two years after the surgery, seventeen patients (eighteen hips) died more than two years postoperatively but were not followed for at least two years, and five hips were lost to follow-up; this left ninety-two hips in eighty-six patients for review. The mean duration of follow-up was five years (range, two to eleven years). For the clinical evaluation, the Charnley modification of the Merle d'Aubigné and Postel scale was used. In addition, preoperative and postoperative Harris hip scores were available for sixty-nine hips. Seventy-eight hips were followed radiographically for two years or more. The focus of the radiographic evaluation was the status of the fixation of the femoral and acetabular components as well as cup wear. RESULTS: Perioperative medical complications occurred in association with 24% (thirty) of the 123 operations, but there were no deaths. The mean Charnley scores for pain and function for the ninety-two hips that were followed clinically for at least two years improved by 3.0 and 1.4 points, respectively. The sixty-nine hips for which preoperative and postoperative Harris hip scores were available had a mean improvement of 42 points, with a mean score of 82 points at the last follow-up evaluation. Mild thigh pain was present in four patients, but it did not limit their activity. There were no femoral component revisions. All of the femoral components were radiographically stable and had bone ingrowth. No acetabular component failed by loosening, but 41% (thirty) of the seventy-three hips with radiographs available for measurement of wear showed polyethylene wear. Of the seventy-eight cups that were followed radiographically for two years or more, 4% (three) were associated with lysis, but none had been revised. CONCLUSIONS: Cementless fixation in the elderly is safe, effective, and durable at the time of two to eleven-year follow-up.

Conservative and semi-invasive modalities for treating bleeding esophageal varices.

Although controversial, pharmacological therapy aimed at controlling acute variceal bleeding is widely used. A combination of intravenous vasopressin and nitroglycerin or glypressin alone with the aim of lowering portal pressure is currently recommended. Immediate endoscopy is mandatory to confirm that the patient is bleeding from varices. When variceal bleeding is detected, the patient should be immediately submitted to sclerotherapy, if expert treatment is available, or have the bleeding controlled by balloon tamponade or by pharmacological means, with subsequent performance of sclerotherapy with the use of a flexible endoscope within 6 to 24 hours, or transportation of the patient to a special center during this time. If bleeding has stopped, sclerotherapy can be performed immediately, or the patient can be observed while appropriate long-term management is planned. Patients who do not respond to immediate or delayed emergency sclerotherapy should be identified early and their suitability for a shunt or devascularisation procedure assessed. There is no question that at least after one or two early or even late recurrences of variceal hemorrhage, surgery should be planned and initiated. Although sclerotherapy is the favored form of emergency treatment, a nonshunting procedure or a portosystemic shunt operation should be recommended and thoroughly evaluated in order to determine whether this may be a preferable therapeutic option in a minority of patients, representing about 20% of all patients bleeding from esophageal varices referred to our institution.

Phytophthora cinnamomi as a Cause of Oak Mortality in the State of Colima, Mexico.

This research identifies the root pathogen Phytophthora cinnamomi as the primary cause of mortality in a 300-ha disease center of mixed oak trees in a native forest in southern Mexico. In increasing order of apparent field resistance to the disease, the major oak species are Quercus glaucoides, Q. peduncularis, and Q. salicifolia. P. cinnamomi was isolated from soil in the affected area from symptomatic trees and was successfully used to perform Koch's postulates on these three oak species. Artificial and natural infections produced vertically elongated discolorations in the outer xylem and distinctive phloem canker lesions with a sharp demarcation line between healthy and affected tissues. In Q. glaucoides there is little evidence that this oak species is able to resist the girdling effects of the phloem lesions, but in Q. peduncularis, and especially in Q. salicifolia, increased production of callus tissue around the phloem canker lesions suggests an active resistance mechanism that may allow these infected trees to survive somewhat longer. This particular incident is unlike other recent reports in other parts of the world of oak mortality caused by P. cinnamomi because the initial appearance of disease in this area is known (just prior to 1987), and it has subsequently expanded to the present area of 300 ha (in 1999) as a distinctive infection locus with periodically advancing infection fronts. This incident is also another dramatic illustration of the potential environmental damage that can result when P. cinnamomi is introduced into a simple forest ecosystem where the major overstory trees are susceptible to infection and are killed.

[Behçet's disease with an onset prior to the appearance of chronic myeloid leukemia]. / Enfermedad de Behçet de inicio previo a la aparición de leucemia mieloide crónica.

The case of a Ph-positive female patient with chronic myeloid leukemia (CML) is reported. The patient presented a cutaneous-mucous picture prior to the appearance of the hemopathy consisting of genitals ulcers, buccal aphthae and nodular cutaneous lesions the study of which demonstrated panniculitis. The lesions improved with the administration of low doses of prednisone and colchicine. The CML evolved to a blastic crisis of a monocytic phenotype at 14 months of diagnosis leading to death of the patient. The cutaneous-mucous picture was catalogued as Becçet disease (BD) according to the criteria of the International Study Group for Behçet Disease. Given the lack of serologic tests or pathognomonic histologic lesions the difficulty in the diagnosis of BD is commented upon and the differential diagnosis of this disease, particularly with respect to the Sweet syndrome, is discussed.

[High-degree malignancy non-Hodgkin's lymphoma simulating a disseminated carcinoma. Presentation of 2 cases]. / Linfoma no hodgkiniano de alto grado de malignidad que simula un carcinoma diseminado. Presentación de dos casos.

Highly malignant non-Hodgkin lymphomas (HM-NHL) may sometimes develop clinical features simulating an epithelial carcinoma with metastatic dissemination. Conventional histopathological study may be insufficient to differentiate between both conditions. Two patients with HM-NHL are reported with a rapid general deterioration; one of them had osteolysis and hypercalcemia. In both cases a diffuse bone marrow infiltration by large sized cells with blastic appearance was found. The initial suspected diagnosis was occult epithelial neoplasia with metastatic dissemination. The morphological study with optic microscopy and the ultrastructural analysis did not establish the origin of these cells. The definitive diagnosis was obtained by immunohistochemical techniques. In both cases, the cells were positive for the CD 45 (common leukocyte antigen) monoclonal antibody (MoAb), and for several MoAbs of lymphoid B differentiation. In one of them, the B lymphoid lineage was confirmed by monoclonal reordering of the gene that synthetises the immunoglobulin heavy chain.

[Clinical significance of dissociated cholestasis as a biological syndrome (author's transl)]. / Significado clínico del síndrome biológico de colestasis disociada.

The case histories of 1200 patients admitted to our hospital over a 20 month period were reviewed to determine the degree, frequency and cause of dissociated cholestasis as a biological syndrome. Patients were divided into two groups: group I with 80 cases, included all patients whose gamma-GT levels were more than 30 mU/ml and serum-bilirubin less than 1.2 mg/ml, with alkaline phosphatase levels between 90-180 mU/ml. Group II included those with alkaline phosphatase levels higher than 180 mU/ml (57 cases). All over incidence of dissociated cholestasis was 13.82%. Main causes in group I were infectious diseases, mainly pneumonias and urinary infections and congestive cardiac failure. In group II, neoplasias such as Hodgkin's disease and epithelial metastases and obstructions of the biliary tract such as vesicular or choledocal litiasis were the main causes. Transaminase levels underwent variable increases according to the different entities, without there being any difference between the two groups. The physiopathology as well as the anatomopathological aspects which could originate the syndrome are discussed.