The 6-min walking distance: long-term follow up in patients with COPD.

The 6-min walking distance (6MWD) test is used in clinical practice and research into patients with chronic obstructive pulmonary disease (COPD). However, little is known about natural long-term change in this parameter. The 6MWD was measured at baseline and then annually for 5 yrs in 294 patients with COPD and its annual rate of decline was determined. Forced expiratory volume in one second (FEV1) was also measured and the relationship between changes in both markers was explored. At baseline, the median 6MWD was 380 m (range 160-600 m). It declined by 19% (16 m.yr(-1)) over the 5 yrs compared with baseline in patients with American Thoracic Society/European Respiratory Society stage III COPD (FEV1 30-50% predicted) and by 26% (15 m.yr(-1)) in patients with stage IV COPD (FEV1 <30% pred). Over the 5-yr follow-up, the proportion of patients with a minimal clinically significant decline of 54 m increased with the severity of the disease. It was 24% in stage II, 45% in stage III, and 63% in stage IV disease. In contrast, the rate of decline of FEV1 was greater in patients with milder airflow obstruction and lesser in patients with lower absolute FEV1 values. In conclusion, the 6-min walking distance test provides increasingly useful information as the severity of chronic obstructive pulmonary disease increases.     

Chronic GVHD in minor salivary glands and oral mucosa: histopathological and immunohistochemical evaluation of 25 patients

BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT). The aim of our study was to identify the most relevant histological features for diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor salivary glands of 25 patients, as well as to evaluate the immunophenotype of the inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic BMT but did not present cGVHD were selected as a control group. The sections were studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD were: hydropic degeneration of the basal layer of the epithelium, apoptotic bodies, lymphocytic infiltration, and focal or total cleavage between the epithelial and connective tissue. In the labial salivary glands (LSG), lymphocytic infiltration, acinar loss and fibrosis were the main alterations. Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T cells and macrophages play important role in the pathogenesis of the disease.     

Basal and metoclopramide-stimulated prolactin (PRL) serum levels in users and non-users of a copper intrauterine device (TCu-380 IUD).

The study was undertaken to analyze the basal and metoclopramide-stimulated serum PRL levels in healthy parous women users (group 1, n = 12) and non-users (group 2, n = 12) of a TCu-380 IUD. All women had regular menses and were studied between days 18 to 22 of their cycle; none had lactated nor regularly ingested any type of medication during the last six months. After a 10-12 hour overnight fast, peripheral venous blood samples were obtained through an indwelling catheter at -30, -15 and 0 minutes and at 60, 90 and 120 minutes after oral metoclopramide (10 mg). There were no significant differences in serum PRL between both groups, in basal levels nor throughout the test, whether analyzing the mean values at each sampling time, the sum of PRL levels from 60-120 minutes, or the peak levels. No correlation was observed between PRL levels and any of the clinical or obstetric characteristics of the women in both groups. Serum progesterone was greater than or equal to 4.0 ng/ml in all women. Thus, the use of alpha TCu-380 IUD did not induce any significant changes in basal nor in stimulated serum PRL levels.     

Dipyridamole and RA-642 inhibit the production of superoxide anion and free radical damage to rat lens.

We studied the effects of dipyridamole and RA-642 on the production of superoxide anions and on oxygen radicals-induced lipid peroxidation in lens tissue homogenates from normal rats and rats given dipyridamole or RA-642 intraperitoneally. Superoxide production was evaluated by phenazine methosulphate (PMS)-induced nitroblue tetrazolium (NBT) reduction and lipid peroxidation by ferrous sulfate and ascorbic acid (FeAs)-induced malondialdehyde (MDA) production. Dipyridamole and RA-642 showed an inhibitory effect on both assays in the experiments with lens tissue homogenates from untreated or treated rats. The extent of inhibition, however, was significantly higher in pyrimidopyrimidinic-treated rats (range of inhibition at different times of incubation was 18% versus 23-57% for dipyridamole and 14% versus 73-80% for RA-642 in the assay of MDA production, and 10% versus 33-37% for dipyridamole and 2.5% versus 11-32% for RA-642 in the assay of NBT reduction). Concentrations of dipyridamole and RA-642 in lens tissue from treated animals could not be determined (less than 0.001 micrograms/mg of tissue). Although both compounds inhibited lipid peroxidation induced by oxygen free radicals, the mechanism of action might include the role of adenosine as a mediator.     

Stage-related increase in the proportion of apoptotic germ cells and altered frequencies of stages in the spermatogenic cycle following gestational, lactational, and direct exposure of male rats to p-nonylphenol.

The cumulative effects of environmental toxicants, for example, the alkylphenol, para-nonylphenol (p-NP) are of concern. Our previous study showed that p-NP reduced several testicular morphometric parameters, including sperm counts. The present study reexamined material collected in that study to determine the mechanistic basis of p-NP action on spermatogenic development in the offspring. Seven-day pregnant Sprague-Dawley rats were treated with vehicle or 100 or 250 mg/kg p-NP through gestation, lactation and afterward directly to all male offspring until 10 weeks of age. Both doses of p-NP significantly (P < 0.02) increased the number of germ cells with in situ end-labeled fragmented DNA (TUNEL positive) by 1.9-fold and 1.7-fold, respectively, and specifically in stages XII-XIV and I-III. TUNEL-labeling was, however, selective, and excluded labeling of basal cells with apoptotic morphology. Cleaved caspase-3 immunohistochemistry strongly labeled basal cells (spermatogonia and early spermatocytes) with condensed marginated chromatin but not degenerate germ cells lacking definitive nuclear material found throughout the epithelium. Only the caspase index (ratio of number of caspase positive to number of degenerate cells) of the 100-mg/kg p-NP group was significantly (p < 0.05) threefold greater than controls. Whereas both doses and either 250 or 100 mg/kg treatment alone significantly (p < 0.002) reduced the frequencies (duration) of stages I-III, VII-VIII, and late VIII-IX (spermiating and recently spermiated tubules), respectively, both doses significantly (p < 0.002) increased the frequencies of stages IV-VI and all stages containing late-stage spermatocytes (XII-XIII) and meiotic cell divisions (XIV). Thus, p-NP, an environmentally persistent xenoestrogen, insidiously alters the spermatogenic cycle and spermatogenic process in male offspring.     

The vertical midface lift. An improved procedure.

We describe a novel procedure for an anatomically-based face lift to correct vertical vectors in the ageing face. It has the advantage of surgical simplicity, minimal tissue removal and minimal risk. It provides an effective readjustment of cheek volume and correction of periorbital hollowness. Natural facial expression is preserved largely because there is no change in the position of the lateral canthus. The cheek is mobilised subperiosteally through a blepharoplasty incision. A second dissection is made via a short temporal incision, to join the infraorbital dissection. A Hagedorn needle is then inserted through a point inferior to the lateral canthus and in line horizontally with the nasal ala. It is passed to the orbital incision, charged with a loop of suture material, and pulled down again to the cheek incision, from where it is pushed back to the orbit to suspend the cheek. The upper border of orbicularis oculi is fixed firmly to the temporalis aponeurosis at the level of the temporal incision. We now frequently use an Endotine Midface device for fixation. Of the first 150 patients, results were excellent or good in 145. This represents a revival of the subperiosteal mask lift, and abandons the use of endoscopic techniques. In spite of its simplicity, the operation involves subperiosteal dissection as well as delicate eyelid surgery that necessitate plastic surgical skill.     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

The course of a case of Maffucci's syndrome

The syndrome of Maffucci is characterized by angioma association of the enchondromatose. It is a relatively rare syndrome. The lesions are evolutived. The treatment is surgical. His pronostic is marqued by high percentage of malign degenerescence.