The sap from Euphorbia peplus is effective against human nonmelanoma skin cancers.

BACKGROUND: The sap from Euphorbia peplus, commonly known as petty spurge in the U.K. or radium weed in Australia, has been used as a traditional treatment for a number of cancers. OBJECTIVE: To determine the effectiveness of E. peplus sap in a phase I/II clinical study for the topical treatment of basal cell carcinomas (BCC), squamous cell carcinomas (SCC) and intraepidermal carcinomas (IEC). METHODS: Thirty-six patients, who had refused, failed or were unsuitable for conventional treatment, were enrolled in a phase I/II clinical study. A total of 48 skin cancer lesions were treated topically with 100-300 µL of E. peplus sap once daily for 3 days. RESULTS: The complete clinical response rates at 1 month were 82% (n = 28) for BCC, 94% (n = 16) for IEC and 75% (n = 4) for SCC. After a mean follow-up of 15 months these rates were 57%, 75% and 50%, respectively. For superficial lesions < 16 mm, the response rates after follow-up were 100% for IEC (n = 10) and 78% for BCC (n = 9). CONCLUSIONS: The clinical responses for these relatively unfavourable lesions (43% had failed previous treatments, 35% were situated in the head and neck region and 30% were > 2 cm in diameter), are comparable with existing nonsurgical treatments. An active ingredient of E. peplus sap has been identified as ingenol mebutate (PEP005). This clinical study affirms community experience with E. peplus sap, and supports further clinical development of PEP005 for the treatment of BCC, SCC and IEC.

The use of radiation therapy for oligoprogressive/oligopersistent oncogene-driven non small cell lung cancer: State of the art.

Oncogene-driven non small cell lung cancer (NSCLC) is a distinct entity in thoracic oncology. The availability of effective target therapies, like EGFR inhibitors or ALK inhibitors, have revolutionized the prognosis of these patients. However, despite an initial response in the majority of patients, drug resistance ultimately occurs. In some cases, this resistance develops in few clonal cells (oligoprogression), so that a local ablation of these resistant deposits could allow to maintain the same systemic therapy and possibly to prolong patients' survival. For these purposes, stereotactic body radiation therapy (SBRT) is an ideal local ablative treatment, because it is effective, non invasive and with limited side effects. In this review, we aim to analyze available clinical data to verify whether SBRT can allow these patients to continue with existing target therapy longer, delay the switch to other systemic therapies and improve their outcome modifying the natural history of the disease.

A MSFD complementary approach for the assessment of pressures, knowledge and data gaps in Southern European Seas: The PERSEUS experience.

PERSEUS project aims to identify the most relevant pressures exerted on the ecosystems of the Southern European Seas (SES), highlighting knowledge and data gaps that endanger the achievement of SES Good Environmental Status (GES) as mandated by the Marine Strategy Framework Directive (MSFD). A complementary approach has been adopted, by a meta-analysis of existing literature on pressure/impact/knowledge gaps summarized in tables related to the MSFD descriptors, discriminating open waters from coastal areas. A comparative assessment of the Initial Assessments (IAs) for five SES countries has been also independently performed. The comparison between meta-analysis results and IAs shows similarities for coastal areas only. Major knowledge gaps have been detected for the biodiversity, marine food web, marine litter and underwater noise descriptors. The meta-analysis also allowed the identification of additional research themes targeting research topics that are requested to the achievement of GES.

Acute coronary vasomotor effects of nifedipine and therapeutic correlates in syndrome X.

In 18 patients (12 women) presenting with effort-induced chest pain and normal coronary angiograms (syndrome X), 10 mg sublingual nifedipine increased the lumen of major coronary arteries (quantitative angiography) by 13 +/- 10% (p less than 0.01), coronary blood flow (thermodilution) by 23 +/- 26% (p less than 0.05), norepinephrine plasma concentration by 60 +/- 42% (p less than 0.01) and decreased the global ST-segment shift during the effort stress test from 8.8 +/- 4.1 to 7 +/- 6.8 mm (p less than 0.03) at comparable maximal workload and at unchanged double product. There was a correlation (positive) of changes in flow with changes in coronary lumen diameter (r = 0.65, p less than 0.01) with ST-segment response to exercise (r = 0.83, p less than 0.001) and with (inverse) norepinephrine plasma concentration (r = -0.70, p less than 0.01); no correlation was found between ST-segment response and changes in arterial lumen diameter. In a few cases, nifedipine did not improve or even worsened the response to exercise; coronary flow was unchanged or decreased and norepinephrine plasma levels were modestly or greatly increased, respectively. After 4 weeks of treatment with nifedipine (10 to 20 mg 4 times daily), the effort ST-segment shift was further decreased to 4.4 +/- 3.5 mm (p less than 0.03) despite a slightly increased double product. Plasma norepinephrine values, as compared to those after acute nifedipine, were decreased by 40% in patients with further improvement and were unchanged in patients whose exercise performance did not vary.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitation of coronary spasm by propranolol in Prinzmetal's angina: fact or unproven extrapolation?

BACKGROUND: Alpha-adrenergic activation enhances coronary vascular tone; beta-blockade leaves alpha-adrenergic vasoconstriction unopposed. Whether beta-adrenergic blockade facilitates coronary spasm in patients with Prinzmetal's angina is unknown. METHODS: Using quantitative angiography, we evaluated the response of normal and narrowed coronary arteries to intravenous propranolol, a cold pressor test (an alpha-stimulus), and the combination of the two in 15 patients with Prinzmetal's (group 1) and in 19 with classic (group 2) angina. From measurements of heart rate, systemic and pulmonary arterial pressures, and left and right ventricular ejection times, we derived the tension-time index per minute as a measure of the oxygen need (O2 demand) of the whole heart. RESULTS: In group 1, cold invariably constricted normal and diseased vessels, and in two patients elicited spasm at sites of significant lesions; these changes did not correlate with those in O2 demand. In group 2, the vasomotor reaction of normal and narrowed vessels in response to cold correlated with the modifications in O2 demand. After propranolol administration, (1) in normal vessels in both groups, the baseline luminal diameter varied in parallel with the changes in myocardial O2 demand; (2) narrowings in group 1 patients invariably dilated and in group 2 the caliber varied according to changes in O2 demand; (3) during cold stimulation, luminal narrowing in group 1 varied in parallel with O2 demand, and, in group 2, vessels were uniformly constricted. CONCLUSION: These results do not support the facilitation of coronary spasm by propranolol in Prinzmetal's angina and support the hypothesis that the contractility of coronary vessels in patients with this form of angina is different from that in the classic form.

7.5% hypertonic saline versus 20% mannitol during elective neurosurgical supratentorial procedures.

This prospective randomized clinical study was designed to compare the effects of equal volumes of 7.5% hypertonic saline solution (HS) or 20% mannitol (M) on brain bulk and lumbar cerebrospinal fluid pressure (CSFP) during elective neurosurgical procedures (aneurysm, arteriovenous malformation, or tumor). After informed consent, 50 American Society of Anesthesiologists physical Status I (ASA I) patients were randomly assigned to M (n = 25) or HS (n = 25) groups. Anesthesia protocol was identical for both, and variables monitored included mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), CSF pressure (CSFP), arterial blood gases (PaCO2 30-35 mm Hg), serum sodium, potassium, and osmolality, and diuresis. The study period started before hypertonic solution administration (T0) and ended at the opening of the dura mater or 60 min after T0. Data were assessed with repeated measures analysis of variance and Student t test with Bonferroni correction (p < or = 0.05). MAP and CVP were the same in the two groups. After treatment, osmolality increased, and the increase at T15 was higher in HS-treated patients [316.6 +/- 9.3 vs. 304.0 +/- 12.0 (SD) mOsmol/kg; p < 0.001]. Sodium decreased after M and increased after HS. During the study, brain bulk was always considered satisfactory. CSFP was not different between M and HS groups and significantly decreased overtime (p = 0.0056) with no difference between treatments. The results of the present study demonstrate that hypertonic saline is as effective as mannitol in reducing the brain bulk and the CSFP during elective neurosurgical procedures under general anesthesia.

Hypertonic saline fluid therapy following brain stem trauma.

Intravenous hypertonic fluid therapy has been proposed to improve secondary ischemic injury after cerebrospinal trauma. We report the case of a 14-year-old boy with vasospasm of the intracranial vertebral arteries and ischemic brain stem damage following head trauma. The patient presented with severe tetraparesis and somatosensory (SSEPs) and brain stem auditory evoked potentials (BAEPs) impairment. The patient was treated with two subsequent hypertonic saline (HS) infusions, 2.7% and 5.4%, respectively, for a period of 48 sp, followed by standard hypervolemic therapy. After the first treatment with 2.7% HS, improvement of SSEPs without neurological improvement was apparent. Relative hypervolemia was subsequently maintained by administration of crystalloids and 20% albumin for 48 h. During standard hypervolemic therapy, no clinical and/or electrophysiological change occurred. The second infusion of 5.4% HS was concomitant with further amelioration of SSEPs and improvement of motor performance. Twelve hours after the second HS infusion, the neurological status returned to preinfusion levels, while SSEPs showed no further changes. BAEPs never changed during fluid therapy. No complication occurred secondary to the infusion of HS. This case report suggests that local improvement of brain stem perfusion following hypertonic fluid therapy accounts for or relevantly contributes to the neurological and SSEPs improvement of the patient.

Surgical tracheostomy versus percutaneous dilatational tracheostomy. A prospective-randomized study with long-term follow-up.

BACKGROUND: To compare surgical tracheostomy (ST) versus percutaneous dilatational tracheostomy (PDT) in terms of complication rates. In particular we specifically studied the late tracheal complications of both methods by means of endoscopic controls of patients up to 6 months after the procedures. DESIGN: prospective-randomized clinical study. SETTING: University-affiliated tertiary care referral hospital. PATIENTS: 50 consecutive translaryngeally intubated patients with respiratory failure were randomized to undergo either ST (25 patients) or endoscopic guided PDT (25 patients). RESULTS: ST was performed in 41+/-14 min versus 14+/-6 min for PDT (p<0.0001). There was no procedure-related death. In the ST group there were no intraoperative complications. In the PDT group 2 intraoperative complications (minor hemorrhages) were observed. In the ST group 9 early postoperative complications occurred: one minor bleeding, 7 stomal infections and one accidental decannulation. In the PDT group only one early postoperative complication (minor bleeding) occurred. Early postoperative complication rates were 36% for ST and 4% for PDT. In the ST group there were no late tracheal complications. In the PDT group 2 late tracheal complications (one segmental malacia and one stenosis at the level of the stoma) were observed. CONCLUSIONS: This study confirms that PDT is a simpler and quicker procedure than ST and that it has a lower rate of early postoperative complications. Late tracheal complications were more frequent, although the difference was not statistically-significant, in the PDT group. Further investigations of long-term outcome following PDT are therefore necessary.

Ultrastructural changes produced in cultured, adriamycin-treated myocardial cells.

The ultrastructural evaluation of the early alterations adriamycin-induced on cultured mice heart cells is reported. The major effects are hypertrophy of the sarcoplasmic reticulum and a market increase of the number and total extension of the gap junctions. These findings are discussed in the light of the information available in the literature.

[Determination of lymphocyte subpopulations in multiple myeloma and monoclonal gammopathies of undetermined significance]. / Determinazione delle sottopopolazioni linfocitarie nel mieloma multiplo e nelle gammopatie monoclonali di significato indeterminato.

By means of monoclonal antibodies, the lymphocyte subpopulation in 12 patients affected by multiple myeloma, 3 by Waldenström's macroglobulinemia, 7 by M.G.U.S. and 8 patients affected by accompanying monoclonal gammopathy have been determined. The group of patients affected by multiple myeloma or Waldenström's macroglobulinemia presented, against control, a significant reduction in the OK T3+ and OK T4+ cell percentage, with a remarkable reduction of the OK T4+/OK T8+ ratio. The OK T8+ cell average, if considered as an absolute value, was not modified in comparison to normal value, while the absolute number of OK T4+ cells was substantially reduced. No significant modifications have been ascertained in the percentage of SIg+ cells. The patients affected by M.G.U.S. did not present significant difference against controls, with regard to the lymphocyte number and the percentage of OK T3+ and OK T4+ cells. On the contrary, a significant increase of the percentage and absolute number of OK T8+ cells was observed. Also in these cases, a significant reduction of the OK T4+/OK T8+ ratio was observed. Finally, the patients affected by accompanying monoclonal gammopathy presented a significant reduction of OK T3+ and OK T8+ cells, with an increase of the percentage of OK T4+ cells and of the OK T4+/OK T8+ ratio.

Fluxplus, a microcomputer program for interactive calculation of 'in vitro' solute fluxes, uptakes and accumulations in studies of intestinal transport.

A new microcomputer program for interactive comparisons, analysis and calculation of in vitro solute transepithelial fluxes and nutrient uptakes and accumulations by intestinal tissues is described. The program is written in Microsoft GWBASIC for the widely distributed IBM-PC. Flux, uptake and accumulation values are obtained by computation from initial sequential data files and stored in sequential or random-orgaized files, depending on the specific process. Computed unidirectional fluxes are saved together with their associate electrical variables. The program calculates univariate statistics for unidirectional and net fluxes, and allows comparisons between selected groups of experiments by using the Student's t-test. An homocedasticity test is also provided. Active uptake or accumulations of solutes are calculated by substracting the predicted diffusive values at a determined concentration to total uptake or accumulation and from this, kinetic parameters are computed. The program was designed to be user-friendly and includes several functions to permit the user to manage and examine stored data. Examples of outputs illustrate applications of the program.

Seasonal fluctuations of DIN/DIP and DON/DOP ratio in the northern Adriatic Sea.

Within the frame of PRISMA 1 "Biogeochemical cycles" research project (April 1995-January 1996) the quantities and the compartments of dissolved nitrogen and phosphorus have been studied in the northern Adriatic basin, considering also the organic pools. The research aimed to provide a better understanding of nutrient availability and to investigate the possible factors which promote the phenomenon of mucilage formation. For this purpose, the availability and the ratios between dissolved nitrogen and phosphorus considering both inorganic and organic fractions have been studied in relation to variations of river outflow and of biological activities. The results obtained reveal the large importance of organic nitrogen (annual average 16 microM) and phosphorus (annual average 0.13 microM) in contributing to the total nutrient availability (annual average total dissolved nitrogen: 29 microM and phosphorus: 0.18 microM) and the pronounced seasonal variability mainly ascribable to biological processes of uptake and remineralization. Furthermore, beside the well documented unbalanced ratio between inorganic nitrogen and phosphorus, the results obtained point out, for the first time, the unbalance also in the organic compartment (ratio between organic nitrogen and phosphorus ranges between 50 and 530), whose consequences might be important in relation to the phenomenon of mucilage formation.

[Rare complication of calculosis of the gallbladder: Bouveret's syndrome]. / Una rara complicanza della calcolosi della colecisti: la sindrome di Bouveret.

The authors report a case, they had the opportunity to observe, of pyloric stenosis, secondary to the migration of two big gall-stones into stomach through a cholecysto-gastric fistula. As the event is extremely rare, they discuss some clinical, diagnostical and therapeutical aspects of same.

Calcifilaxis, a propósito de un caso / Calciphylaxis, about a case

Resumen La calcifilaxis es un síndrome caracterizado por la calcificación de la pared media de las arteriolas de pequeño y mediano calibre de dermis y tejido celular subcutáneo, que se caracteriza clínicamente por úlceras necróticas, intensamente dolorosas, que afectan sobre todo miembros inferiores. Existen factores de riesgo para su desarrollo, como insuficiencia renal crónica, hiperparatiroidismo, sexo femenino, raza caucásica, diabetes, uso de anticoagulantes, entre otros. Si bien no existe un protocolo estandarizado para su tratamiento, se ha propuesto el uso del tiosulfato sódico como primera elección. Se presenta el caso de una paciente de sexo femenino de 75 años de edad con diagnóstico de calcifilaxis.

Abstract Calciphylaxis is a syndrome characterized by calciphication of the media of small and medium vessels of dermis and subcutaneous celular tissue, clinically characterized by extremely painful, necrotic ulcers, that affects especially lower limbs. There are risk factors for its development, such as renal failure, hyperparathyroidism, female gender, caucasian race, diabetes, use of anticoagulants, among others. Although there is not a standarized protocol for the treatment, it has been proposed the use of sodium thiosulfate as first line. We report a case of a woman of 75 years old with calciphylaxis.

Muscle enzyme elevation after elective neurosurgery.

BACKGROUND: Serum creatine kinase and myoglobin elevation has been described involving muscle manipulation after surgery and also after bariatric, urologic and gynaecologic procedures. It encompasses a wide range of severity, reflecting in the worst cases true rhabdomyolysis. We occasionally noted creatine kinase elevations after intracranial neurosurgery, an occurrence that has not yet been described. To assess whether the issue of postoperative muscle enzyme elevation is relevant to neurosurgery, we prospectively measured serum creatine kinase and myoglobin in a series of neurosurgical patients submitted to craniotomy. MATERIALS AND METHODS: We studied 30 patients aged 22-69 yr submitted to craniotomy. Blood samples were taken prior to the procedure, at the end of anaesthesia and on the first, second and third postoperative days. Blood was checked for creatine kinase, myoglobin, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine and serum electrolytes. We recorded the patient's age, sex, height, weight and body mass index. Throughout surgery, we recorded the highest and the lowest body temperature and sampled the mean arterial pressure at 5 min intervals. We performed backwards stepwise logistic regression analysis to identify the elements that best correlate with the development of cell muscle damage. RESULTS: On the first postoperative day creatine kinase peaked from baseline (305 (107-1306) UI L(-1) vs. 59 (42-94) UI L(-1); P < 0.001) while myoglobin rose significantly from baseline to the end of surgery (70 (42-147) ng mL(-1) vs. 36 (3044) ng mL(-1); P = 0.002). Logistic regression showed that length of surgery was the only factor clearly influencing peak creatine kinase (P < 0.001; R2 0.7) and myoglobin (P = 0.011; R2 0.41) concentration. CONCLUSIONS: Creatine kinase and myoglobin elevation may occur after intracranial neurosurgery. In our series, length of surgery was a risk factor.

In situ monitoring of film deposition with an ellipsometer based on a four-detector photopolarimeter.

Ellipsometry is a sensitive and noninvasive technique for the characterization of thin films. A recently developed ellipsometer, based on the four-detector photopolarimeter, was arranged outside a UHV chemical vapor deposition chamber for the in situ monitoring of film growth processes. The instrument showed a sensitivity in the submonolayer range when used to follow the growth of germanium thin films deposited on silicon substrates. As the main instrument drawback is represented by the need to have precise alignment, an effective positioning procedure was developed to obtain a positioning error smaller than 0.1°.

Fatal Kikuchi-Fujimoto disease: the lupus connection.

Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotizing lymphadenitis found mainly in young women. Patients typically present with cervical lymphadenopathy and fever and follow almost always a benign course with excellent outcomes. The etiology of KFD remains unknown and controversial although several viruses have been associated with this disease. One theory proposes that KFD may be a self-limiting form of systemic lupus erythematosus (SLE). This theory is strongly supported by the fact that microscopic features of KFD can be very similar to those found in lupus lymphadenitis. Despite its usually benign course, several cases with fatal outcomes have been reported. We report here a case of clinically aggressive KFD, which featured several autoimmune-related events and resulted in a fatal outcome. Autopsy studies showed characteristic findings of SLE, which suggests a remarkable link between SLE and KFD. Early and intensive immunosuppressive treatment may be the only option for patients who develop very aggressive forms of KFD in order to avoid a fatal outcome.