Diagnostic accuracy of contrast-enhanced computed tomography for assessment of mandibular and medial retropharyngeal lymph node metastasis in dogs with oral and nasal cancer.

The diagnostic accuracy of contrast-enhanced CT for detection of cervical lymph node metastasis in dogs is unknown. The purpose of this retrospective, observational, diagnostic accuracy study was to assess the efficacy of CT for detection of mandibular and medial retropharyngeal lymph node metastasis in dogs. Histopathology of dogs with cancer of the head, CT and bilateral mandibular and medial retropharyngeal lymphadenectomy was reviewed. A single radiologist measured lymph nodes to derive short axis width and long-short axis ratios. Two blinded radiologists separately assessed lymph node margins, attenuation and contrast enhancement and each provided a final subjective interpretation of each node site as benign or neoplastic. Where radiologists' opinions differed, a consensus was reached. Sensitivity, specificity and accuracy were calculated for mandibular and medial retropharyngeal sites. Agreement between radiologists was assessed. Fisher's exact test and the Kruskal-Wallis H-test were used to assess associations between variables. Forty-one primary tumours were recorded in 40 dogs. Metastasis to mandibular or retropharyngeal lymph nodes occurred in 16 out of 40 dogs (43/160 nodes). Agreement between radiologists was almost perfect for margination, attenuation and enhancement, strong for interpretation of mandibular lymph node metastasis, and weak for interpretation of medial retropharyngeal lymph node metastasis. Sensitivity of CT was 12.5% and 10.5%, specificity was 91.1% and 96.7%, and accuracy was 67.5% and 76.3% for mandibular and medial retropharyngeal lymph nodes respectively. No individual CT findings were predictive of nodal metastasis. Given the low sensitivity of CT, this modality cannot be relied upon alone for assessment of cervical lymph node metastasis in dogs.

Lipid subclasses profiles and oxidative stress in aggressive periodontitis before and after treatment.

BACKGROUND AND OBJECTIVE: Associations between dyslipidaemia, oxidative stress and periodontitis have emerged in recent years. However, there is a lack of studies investigating these associations in aggressive periodontitis (AgP) cases. The aim of this study was to investigate the lipid and oxidative stress profiles in patients with AgP, and to relate them to clinical variables and interleukin (IL)-6 genetic variants. MATERIAL AND METHODS: Twelve non-smoking Caucasian patients with AgP selected based on their IL6 haplotypes underwent periodontal non-surgical and surgical treatment. Peripheral blood samples taken at baseline and at six different time-points after treatment were processed to determine IL-6 circulating levels, lipid profiles (cholesterol, triglycerides, high-density lipoprotein [HDL] and low-density lipoprotein [LDL] subclasses) and oxidative stress markers (glutathione and total lipid hydroperoxide levels). RESULTS: HDLs were the most prevalent lipoproteins, followed by intermediate-density lipoprotein, very-low-density lipoprotein and LDL. The LDL subclasses consisted mainly of the less atherogenic large LDL. The lipid profile did not consistently change after treatment up to 3 mo after surgery. Periodontal disease severity was associated with LDL levels and size. The IL6 haplotypes were associated with total cholesterol, triglycerides, HDL and LDL subclasses after adjusting for confounders. IL-6 circulating levels were associated with both very-low-density lipoprotein and lipid hydroperoxide levels. CONCLUSION: Based on these data, we conclude that both periodontal disease severity and IL6 haplotypes may influence lipid profiles in AgP.

Relationship between weakness and phase angle in advanced cancer patients with fatigue.

OBJECTIVE: This study aims to determine the relationship between weakness and bioimpedance analysis (BIA)-derived phase angle in a population of untreated cancer patients with fatigue. METHODS: We prospectively evaluated 41 treatment-naive cancer patients of several origins that presented with performance status 1-2, weight loss >5% in the last 6 months, and Fatigue Numeral Scale score >4. Weakness was considered a physical component of the multidimensional fatigue syndrome and was evaluated through several parameters utilizing hand grip strength technique by dinamometry. The same assessment was also performed on a healthy control population (n = 20). BIA-derived phase angle was also determined by BIA. RESULTS: Compared to healthy controls, cancer patients exhibited significant differences in all the parameters: median fatigue was 6 (range 5-9), evaluated maximal strength mean was 27 ± 10.71 vs. 42 ± 10.74 kg (p < 0.0001 for patients vs. control, respectively), and muscle strength difference (max-min muscle strength) was also statistically different (p < 0.0001). We also determined parameter associations within the patient population. We found statistical significant correlations between median phase angle score and endurance muscle with percentage of weight loss (r = 0.43, p = 0.03) for head and neck cancer patients, and in non-small cell lung cancer patients, grip work correlated significantly with normal or decreased phase angle (r = 0.85), p = 0.006 (Spearman Rank Correlation). CONCLUSIONS: Weakness could be correlated with normal or decreased phase angle in a population with ambulatory advanced cancer with fatigue naive of treatment. We also found a significant relationship between median phase angle score and endurance muscle with percentage of weight loss in the subpopulation of patients with head and neck carcinoma.

Spatio-temporal patterns of diarrhoeal mortality in Mexico.

Diarrhoeal mortality rates in Mexican children dramatically declined during the 1980s and 1990s, concomitant with a temporal shift in peak deaths from summer to autumn-winter. The spatial dynamics of these patterns have not previously been studied. We first describe the seasonal features of paediatric diarrhoeal mortality in Mexico as a whole, then across individual states. While no geographical gradients in the magnitude of diarrhoeal mortality rates have been detected in recent years, we identified a distinct spatial pattern in the timing of peak mortality rate. In the 1980s the summer peak mortality was earliest around Mexico's capital and later in states to the southeast and northwest. Our results suggest that the direction and timing of those annual waves are related to the mean monthly precipitation and mean daily temperature. This pattern has disintegrated in recent years as the summer peak has diminished.

Identification of three distinguishable phenotypes in golden retriever muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a human disease characterized by progressive and irreversible skeletal muscle degeneration caused by mutations in genes coding for important muscle proteins. Unfortunately, there is no efficient treatment for this disease; it causes progressive loss of motor and muscular ability until death. The canine model (golden retriever muscular dystrophy) is similar to DMD, showing similar clinical signs. Fifteen dogs were followed from birth and closely observed for clinical signs. Dogs had their disease status confirmed by polymerase chain reaction analysis and genotyping. Clinical observations of musculoskeletal, morphological, gastrointestinal, respiratory, cardiovascular, and renal features allowed us to identify three distinguishable phenotypes in dystrophic dogs: mild (grade I), moderate (grade II) and severe (grade III). These three groups showed no difference in dystrophic alterations of muscle morphology and creatine kinase levels. This information will be useful for therapeutic trials, because DMD also shows significant, inter- and intra-familiar clinical variability. Additionally, being aware of phenotypic differences in this animal model is essential for correct interpretation and understanding of results obtained in pre-clinical trials.

Vascular involvement in diabetic subjects with ischemic foot ulcer: a new morphologic categorization of disease severity.

OBJECTIVES: Arteriographic lesions of diabetic subjects with critical limb ischemia (CLI) and ischemic foot ulcer were reviewed retrospectively, to provide new criteria for stratification of these patients on the basis of their vascular involvement. PATIENTS: In 417 consecutive CLI diabetic subjects with ischemic foot ulcer undergoing lower limb angiography, lesions were defined as stenosis or occlusion, localization, and length (<5 cm, 5-10 cm, >10 cm). In a subgroup of 389 subjects, foot arteries also were evaluated. Patients then were categorized into 7 classes of progressive vascular involvement based on angiographic findings. RESULTS: Of the 2893 found lesions (55% occlusions) 1% were in the iliac arteries, whereas 74% were in below-the-knee (BTK) arteries. Sixty-six % of all BTK lesions were occlusions, and 50% were occlusions >10 cm (p<0.001 vs proximal segments). Occlusions of all BTK were present in 28% of patients, although there was patency of at least one foot artery in 55% of patients. The morphologic Class 4 (two arteries occluded and multiple stenoses of tibial/peroneal and/or femoral/popliteal vessels) was the most common (36%). An inverse correlation between morphologic class and TcPO2 was observed (r=-0.187, p=0.003). CONCLUSIONS: In CLI diabetic subjects with ischemic foot ulcer, the vascular involvement is extremely diffuse and particularly severe in tibial arteries, with high prevalence of long occlusions. A new morphologic categorization of these patients is proposed.

Osteotomia proximal da ulna associada à distração do olécrano com utilização de fixador externo linear no tratamento da não união do processo ancôneo no cão

O artigo não apresenta resumo.

Extensive use of peripheral angioplasty, particularly infrapopliteal, in the treatment of ischaemic diabetic foot ulcers: clinical results of a multicentric study of 221 consecutive diabetic subjects.

OBJECTIVE: To evaluate the feasibility, technical effectiveness and limb salvage potential of percutaneous transluminal angioplasty (PTA), particularly infrapopliteal, in diabetic subjects with ischaemic foot ulcer. DESIGN: Intervention study with PTA in consecutive series. SETTING: Six Diabetology Foot Centres and one Cardiovascular Catheterization Laboratory in Italy. SUBJECTS: Two hundred and twenty-one consecutive diabetic subjects hospitalized for ischaemic foot ulcer. INTERVENTION: Peripheral arterial occlusive disease (PAOD) was investigated by means of foot pulses assessment, ankle-brachial-index (ABI), transcutaneous oxygen tension (TcPO2) and duplex scanning. If non-invasive parameters suggested PAOD, angiography was performed and a PTA was carried out during the same session. MAIN OUTCOME MEASURES: PTA feasibility, improvement of ABI and TcPO2, limb salvage rate, clinical recurrence. RESULTS: On angiography, two patients had stenoses which were <50% of the vessel diameter. PTA was performed in 191 (85.3%) of the 219 subjects with stenoses >50%, even when longer than 10 cm and/or multiple/calcified. In 11 patients (5.8%) PTA was performed in the proximal axis exclusively, in 81 (42.4%) patients in the infrapopliteal axis exclusively and in 99 (51.8%) in both the femoropopliteal and infrapopliteal axis. Both ABI and TcPO2 improved significantly after PTA (P < 0.0001). Clinical recurrence occurred in 14 subjects: 10 of whom underwent a second successful PTA. Of the 191 patients who underwent PTA, 10 (5.2%) underwent an above-the-ankle amputation. CONCLUSIONS: PTA, including infrapopliteal, is feasible in most diabetic subjects with ischaemic foot ulcer and is effective for foot revascularization. Clinical recurrence was infrequent and the procedure could successfully be repeated in most cases. In subjects treated successfully with PTA the above-the-ankle amputation rate was low. PTA should be considered as the revascularization treatment of first choice in all diabetic subjects with foot ulcer and PAOD.

Cáncer de mama y 153 Samario EDTMP / Breast cancer and Samarium 153 EDTMP

Objetivo: evaluar la toxicidad y eficacia terapéutica del Sm153 EDTMP en pacientes con cáncer de mama avanzado y dolor producido por metástasis óseas con reacción osteoblástica y su repercusión centellográfica y de laboratorio. Materiales y métodos: 54 pacientes (edad promedio: 62) con metástasis óseas y dolor con Samario en dosis de 0,5; 1 y 1,5 mCi/kg; 5 pacientes fueron retratadas. Se realizó control clínico y laboratorio al inicio, semanalmente durante el primer mes y luego mensualmente. Se correlacionaron centellografías óseas pre y post tratamiento. De las 54 pacientes, 21 (primer grupo) recibieron 0,5 mCi/kg; 29 (segundo grupo) 1 mCi/kg y 4 pacientes (tercer grupo) 1,5 mCi/kg. Resultados: la respuesta positiva al tratamiento se valoró mediante la atenuación o desaparición del dolor y la disminución del uso de analgésicos. El primer grupo tuvo una respuesta positiva del 76 por ciento, el segundo de 83 por ciento y el tercero de 75 por ciento. La duración de la respuesta varió entre 3 y 9 meses. La toxicidad más frecuente fue trombocitopenia y luego leucopenia, ambas fueron reversibles y presentaban relación directa a la dosis administrada. La correlación centellográfica muestra una disminución de la intensidad de fijación en las pacientes retratadas. Conclusiones: el uso de radiofármacos con afinidad ósea como el Sm resulta ser una alternativa, dada su eficacia y accesibilidad de costos. En nuestro grupo de pacientes tratadas con una dosis de 1 mCi/kg se alcanzó una respuesta del 83 por ciento sin mayor aaumento de la toxicidad, la cual fue reversible

Cáncer de mama y 153 Samario EDTMP / Breast cancer and Samarium 153 EDTMP

Objetivo: evaluar la toxicidad y eficacia terapéutica del Sm153 EDTMP en pacientes con cáncer de mama avanzado y dolor producido por metástasis óseas con reacción osteoblástica y su repercusión centellográfica y de laboratorio. Materiales y métodos: 54 pacientes (edad promedio: 62) con metástasis óseas y dolor con Samario en dosis de 0,5; 1 y 1,5 mCi/kg; 5 pacientes fueron retratadas. Se realizó control clínico y laboratorio al inicio, semanalmente durante el primer mes y luego mensualmente. Se correlacionaron centellografías óseas pre y post tratamiento. De las 54 pacientes, 21 (primer grupo) recibieron 0,5 mCi/kg; 29 (segundo grupo) 1 mCi/kg y 4 pacientes (tercer grupo) 1,5 mCi/kg. Resultados: la respuesta positiva al tratamiento se valoró mediante la atenuación o desaparición del dolor y la disminución del uso de analgésicos. El primer grupo tuvo una respuesta positiva del 76 por ciento, el segundo de 83 por ciento y el tercero de 75 por ciento. La duración de la respuesta varió entre 3 y 9 meses. La toxicidad más frecuente fue trombocitopenia y luego leucopenia, ambas fueron reversibles y presentaban relación directa a la dosis administrada. La correlación centellográfica muestra una disminución de la intensidad de fijación en las pacientes retratadas. Conclusiones: el uso de radiofármacos con afinidad ósea como el Sm resulta ser una alternativa, dada su eficacia y accesibilidad de costos. En nuestro grupo de pacientes tratadas con una dosis de 1 mCi/kg se alcanzó una respuesta del 83 por ciento sin mayor aaumento de la toxicidad, la cual fue reversible (AU)

A randomised phase II study of oxaliplatin alone versus oxaliplatin combined with 5-fluorouracil and folinic acid (Mayo Clinic regimen) in previously untreated metastatic colorectal cancer patients.

The aim of this study was to examine the efficacy and safety of both oxaliplatin as a single agent and oxaliplatin in combination with dailyx5 bolus 5-fluorouracil and folinic acid (5-FU/FA, Mayo clinic regimen) in the first-line treatment of metastatic colorectal cancer (CRC) patients. 73 advanced CRC patients were randomised to receive either oxaliplatin 85 mg/m(2) every 2 weeks (35 patients), or the same treatment combined with 5-FU 425 mg/m(2)/day and FA 20 mg/m(2)/dayx5 days every 4 weeks (38 patients). Treatment was continued until disease progression or unacceptable toxicity. All patients had documented inoperable disease and no previous chemotherapy for advanced disease. Based on the investigators' assessment of best response, objective response rate was 9% (95% confidence interval (CI) 2-24%) in the oxaliplatin arm, and 45% (95% CI 27-64%) in the oxaliplatin+5-FU/FA arm. Median progression-free survival (PFS) was 2 months (95% CI 1.7-2.4 months) in the oxaliplatin arm and 3.9 months (95% CI 2.9-5 months) in the oxaliplatin+5-FU/FA arm. Severe neutropenia was seen in 23% of patients in the oxaliplatin+5-FU/FA arm, and none in the oxaliplatin arm. There were two treatment-related deaths, both in the oxaliplatin+5-FU/FA arm. In the oxaliplatin+5-FU/FA arm, severe diarrhoea, vomiting and stomatitis were seen in 34, 14 and 14% of the patients, respectively. In conclusion, oxaliplatin at a dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limited activity in metastatic CRC, while the combination of this treatment with the full-dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day+FA 20 mg/m(2)/dayx5 days every 4 weeks), although active, was unfeasible due to a high level of myelosuppression and gastrointestinal toxicity. Alternative lower dosing or other regimens are to be explored to ascertain the value of bolus 5-FU/FA combined with oxaliplatin.

Effectiveness and safety of a nonremovable fiberglass off-bearing cast versus a therapeutic shoe in the treatment of neuropathic foot ulcers: a randomized study.

OBJECTIVE: To evaluate and compare the rate of reduction of the surface area of neuropathic plantar ulcers in diabetic patients treated with nonremovable rigidity-differentiated fiberglass off-bearing casts or a cloth shoe with a rigid sole with unloading alkaform insoles. The secondary aim was to evaluate the side effects and degree of patient acceptance of treatment. RESEARCH DESIGN AND METHODS: Fifty diabetic patients with neuropathic plantar ulcers were consecutively enrolled and randomized to one of two treatment groups. Of the 50 patients, 24 were treated with a specialized cloth shoe with a rigid sole and an unloading alkaform insole (shoe group), and 26 patients were treated with a nonremovable off-bearing fiberglass cast (cast group). All patients in both study groups returned to the clinic for weekly control visits. Their ulcers were treated with a standard dressing. Tracings of the ulcer area using a transparent dressing were performed on the day of entry to the study and after 30 days of treatment. The presence of new ulcerations caused by the use of the pressure-relief apparatus was recorded. Patient acceptance of the treatment was measured using a visual analog scale. RESULTS: At the end of the treatment period, an 8.3% increase of the ulcer area was observed in two patients in the shoe group, whereas in the cast group, no patient presented an increase. The reduction of the ulcer area was statistically more rapid in the cast group (Mann-Whitney test, P = 0.0004). Furthermore, the number of ulcers completely healed at the 30-day time point was 13 (50%) in the cast group and 5 (20.8%) in the shoe group (P = 0.03). In both groups, no side effects were recorded. The average score +/- SD of patient acceptance was 91.15 +/- 9.9 in the shoe group and 88.33 +/- 17.3 (NS) in the cast group. CONCLUSIONS: Our study has shown a significant difference in the speed of the reduction of neuropathic plantar ulcers treated with a fiberglass cast compared with a specialized cloth shoe. The use of fiberglass material with variable rigidity has also shown two important results: the elimination of side effects including ulcers caused by the cast, and high patient acceptance. These data show that the use of off-bearing casts made with fiberglass bandages of variable rigidity is the elective treatment of neuropathic plantar ulcers.

Influence of abdomen on respiratory mechanics in supine rabbits.

Previous studies showed that abdominal evisceration has no effect on respiratory system compliance. We hypothesized that this could be related to lung distortion in eviscerated animals. Methods were developed for continuous recording of pleural pressure (Ppl) at various sites over the costal (co) and diaphragmatic lung surface (di) in acutely and chronically instrumented rabbits. We compared deltaPpl,co and deltaPpl,di recorded at mid-lung height during inflations in anesthetized, paralyzed supine rabbits before and after evisceration. Cranial and caudal deltaPpl.co were the same under all conditions. In intact animals, deltaPpl.co and deltaPpl,di were equal at all inflation volumes, whilst in eviscerated animals, deltaPpl,di were smaller than deltaPpl,co, the difference increasing with lung inflation. At any given volume, rib cage circumference (Crc) was smaller after evisceration, but the Crc deltaPpl,co relationship remained unchanged. These results are indicative of non-uniform lung expansion after evisceration and are consistent with model predictions based on cylindrical deformation and lung stress-strain relationship. This deformation should mimic the effect of a reduced lung compliance, keeping respiratory system compliance of eviscerated animals nearly normal. Similar deformation should have occurred also in intact rabbits during strong inspiratory efforts and in the erect posture, because lower Ppl,di than Ppl,co values were observed at the same lung height under these conditions.

Effect of kynurenine on tryptophan-albumin binding in human plasma.

Increased plasma free tryptophan levels have been reported in cancer patients and causally associated to the presence of anorexia. The pathogenesis of this occurrence is yet to be completely understood. Kynurenine is a metabolite of tryptophan, and has been reported increased in plasma during tumor growth. Because of the similarities between tryptophan and kynurenine we speculate that their rise in the presence of a tumor might be causally related. To test this hypothesis, we performed a series of in-vitro studies, showing that kynurenine supplementation reduces the amount of tryptophan bound to albumin, and thus, by competition, increases free tryptophan levels. The likely clinical consequences of these findings are discussed.

Tratamiento conservador del cáncer de vejiga invasor: combinación de cirugía + radioquimioterapia / Preservation treatment of the invasive bladder cancer: surgery + chemoradiation

Un 50 por ciento de los pacientes con cáncer de vejiga invasor (CVI), cistectomizados viven a 5 años. La radioterapia (RT), quimioterapia (QT) y cirugía se han combinado a fin de preservar el órgano mejorando estos resultados. Entre 10/89 y 6/94 se realiza en el Instituto Angel H. Roffo un protocolo multidisciplinario para el tratamiento del CVI, reportándose sus resultados. Material y Métodos: Ingresan 34 pacientes (ps), 29 evaluables. Hombres 28 ps, Mujeres 1 p. Edad x: 60 a. Transicional 26 ps, otros 3 ps G2: 6 ps, G3: 18 ps, G4: 4 ps. P2: 20 ps, P3: 7 ps, P4: 1 ps. RTU: Completa 14 ps (48,2 por ciento), Incompleta 15 ps (51,7 por ciento). Seguimiento x: 30 ms (5-79 ms). Tratamiento: Cisplatino 100 mg/m2/días 1-21 y 42. Radioterapia días 21-63: DT 6000r. Se analizaron factores predictores de Sobrevida (SV) y Sobrevida Libre de Enfermedad (SLE) mediante test de Kaplan Meier, uni y multivarianza. Resultados: Sin Evidencia de Enfermedad (SEE) 18 ps (62 por ciento). Con Evidencia de Enfermedad (CEE) 11 ps (38 por ciento) Quince ps (51,7 por ciento) conservaron su vejiga. Sobrevida (SV) x: 30 ms (10-79). Los pacientes CEE tuvieron en general mala evolución. Variables pronósticas: a) Respuesta al tratamiento (RTA): SV (p < 0,000) y SLE (p 0,036) (multivarianza). Conclusiones: 1) La combinación de RTU+QT+RT es factible y poco tóxica. 2) Conservación vesical: 51,7 por ciento, viven SEE: 48 por ciento. 3) La RTA es variable independiente para SV (p 0,000) y SLE (p 0,000). 4) El estadío (P) aparece como factor pronóstico en multivarianza (p 0,036)

Tratamiento conservador del cáncer de vejiga invasor: combinación de cirugía + radioquimioterapia / Preservation treatment of the invasive bladder cancer: surgery + chemoradiation

Un 50 por ciento de los pacientes con cáncer de vejiga invasor (CVI), cistectomizados viven a 5 años. La radioterapia (RT), quimioterapia (QT) y cirugía se han combinado a fin de preservar el órgano mejorando estos resultados. Entre 10/89 y 6/94 se realiza en el Instituto Angel H. Roffo un protocolo multidisciplinario para el tratamiento del CVI, reportándose sus resultados. Material y Métodos: Ingresan 34 pacientes (ps), 29 evaluables. Hombres 28 ps, Mujeres 1 p. Edad x: 60 a. Transicional 26 ps, otros 3 ps G2: 6 ps, G3: 18 ps, G4: 4 ps. P2: 20 ps, P3: 7 ps, P4: 1 ps. RTU: Completa 14 ps (48,2 por ciento), Incompleta 15 ps (51,7 por ciento). Seguimiento x: 30 ms (5-79 ms). Tratamiento: Cisplatino 100 mg/m2/días 1-21 y 42. Radioterapia días 21-63: DT 6000r. Se analizaron factores predictores de Sobrevida (SV) y Sobrevida Libre de Enfermedad (SLE) mediante test de Kaplan Meier, uni y multivarianza. Resultados: Sin Evidencia de Enfermedad (SEE) 18 ps (62 por ciento). Con Evidencia de Enfermedad (CEE) 11 ps (38 por ciento) Quince ps (51,7 por ciento) conservaron su vejiga. Sobrevida (SV) x: 30 ms (10-79). Los pacientes CEE tuvieron en general mala evolución. Variables pronósticas: a) Respuesta al tratamiento (RTA): SV (p < 0,000) y SLE (p 0,036) (multivarianza). Conclusiones: 1) La combinación de RTU+QT+RT es factible y poco tóxica. 2) Conservación vesical: 51,7 por ciento, viven SEE: 48 por ciento. 3) La RTA es variable independiente para SV (p 0,000) y SLE (p 0,000). 4) El estadío (P) aparece como factor pronóstico en multivarianza (p 0,036) (AU)

Developmental study of ultrastructural and biochemical changes in isolated chick brain microvessels.

The morphology of the endothelial junctions, the expression of the alkaline phosphatase (ALKP) and gamma-glutamyltranspeptidase (GGT) activities, and the transport systems for neutral amino acids (NAA) and for d-glucose were studied in parallel in isolated microvessels from the brains of 9-, 12-, and 21-day chick embryos and 30-day chickens using freeze-fracturing and biochemical techniques. In the 9-day embryos, the endothelium junctional plasma membranes show alignments of discrete intramembrane particles (Imps) on the replica P-faces. In the 12-day embryos, the junctional membranes show short fibrils of loosely interconnected fused Imps. In the 21-day embryos, the junction is characterized by simple networks, and in the 30-day chickens, by very dense meshworks of continuous, fibrillary strands. In early embryonic life, the ALKP activity is expressed at high levels, more markedly in the microvessels than in the whole brain. ALKP progressively declines in later embryos and even more in adulthood, when the activity is fivefold higher in the microvessels than in the whole brain. No GGT activity is expressed in either embryonic or adult microvessels. The transport systems for NAA and for d-glucose are most active in 12-day embryonic microvessels, and progressively less expressed by the 21st day and in the adult. The results taken as a whole suggest a close relationship between the morphological and the metabolic maturation of the endothelial barrier of cerebral vessels.

Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer.

From January 1990 to April 1993, 60 oesophageal cancer patients were enrolled in a protocol of non-surgical treatment that consisted of induction chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy consisted of cisplatin 40 mg/m2 intravenous bolus days 1, 2, 14, 15; 24 h continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2 days 1 and 14; leucovorin 20 mg/m2 days 1 and 14 given before and with 5-FU; bleomycin 30 UI days 1 and 14; mitomycin C 10 mg/m2 day 14. Concurrent chemoradiotherapy consisted of 60 Gy (6 weeks) from day 21 and cisplatin 70 mg/m2 days 28, 42 and 56; leucovorin 20 mg/m2 followed by 5-FU 425 mg/m2 days 28, 35, 42, 49 and 56. Complete response occurred in 44 of 55 evaluable patients (80%). The median survival is 32 months; the actuarial survival at 40 months is 35% (CI 18-53). These results appear improved over those reported with surgery or radiation alone, and suggest that organ preservation as a secondary treatment goal should be vigorously investigated.

Nucleus reticularis thalami and neocortical paroxysms in the rat.

The role of the nucleus reticularis thalami in spike-wave discharges in rats with genetic absence epilepsy has already been demonstrated. This study further investigated the role of the nucleus reticularis thalami in paroxysmal synchronizations in Sprague-Dawley rats; this strain shows no propensity to epileptic activity. Electroencephalographic patterns were followed in chronically implanted, unrestrained rats. After both electrolytic and chemical unilateral lesions, stereotaxically placed in the anterolateral sectors of this nucleus (verified post mortem), abnormal electroencephalographic rhythms (high-voltage polyspikes and spike-wave complexes) were recorded from the frontoparietal cortex, primarily in the contralateral hemisphere. Stereotyped discharges at 3 Hz developed progressively from multiple spikes within the alpha frequency range through the lengthening of the wave component. The excessive synchronized activity recorded from the intact hemisphere was of greater amplitude and occurred slightly earlier than from the lesioned hemisphere. These EEG patterns were associated with behavioural manifestations closely resembling those seen during absence seizures in humans. Bilateral lesions did not induce paroxysmal activity, both hemispheres being characterized by dominant delta/theta activity without signs of EEG-synchronized sleep. The seizures may thus have been due to disinhibition of the contralateral reticularis nucleus, recently shown to project to the reticularis nucleus of the other side in rats. This working hypothesis is supported by callosal cuts. The results indicate that the reticular neurons exert a control over neocortical paroxysmal activity even in animals which do not present genetic absence epilepsy.