Intra-aortic injection of myoblasts in mdx mice: genetic and technetium-99m cell labeling and biodistribution.
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Biomedical subjects
Publications and source records attributed to F Colombo.
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The aim of this study was the retrospective evaluation of the effectiveness of cis/carboplatin + vinorelbine +/- radiotherapy in 118 patients with advanced non small cell lung carcinoma (NSCLC). To evaluate the response, pts were divided into three groups: a) Stage III pts. who received both chemotherapy and radiotherapy treatment (RC + RP = 43.75%, median survival 16.25 months); b) Stage III pts. who underwent only CT because RT was contraindicated (RC + RP = 21.95%, median survival 12.7 months); c) Stage II pts treated with CT alone (RC + RP = 20%, median survival = 12.1 months). Toxicity was mild. The results of the present study, both in terms of response rate and survival, confirm the effectiveness of the combination cis/carboplatin + vinorelbine +/- radiotherapy as palliative treatment of advanced NSCLC.
In the last decade, several clinical trials in patients with, or recovering from, acute myocardial infarction (AMI) have evaluated the role of calcium antagonists in affecting patients' prognosis. Results have been disparate, with evidence of possible harm, no effect, or some benefit, depending on the agent used. We evaluated how the evidence from these trials has influenced the pattern of prescription of calcium antagonists and assessed the important determinants of use of these agents in patients after AMI. We analyzed retrospectively the prescription of calcium antagonists at discharge in all patients recovering from AMI enrolled in 3 large randomized clinical trials (Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto-1 [GISSI-1], GISSI-2, and GISSI-3) during the last 10 years. A progressive decrease in prescriptions for calcium antagonists was evident, from 47.2% in GISSI-1 to 35.1% in GISSI-2 to 19.0% in GISSI-3 (p<0.001). The presence of post AMI angina, history of hypertension, and occurrence of reinfarction were associated with a higher usage of calcium antagonists, whereas the use of beta blockers at discharge was a major independent negative determinant. Use of calcium antagonists for secondary prevention after AMI (i.e., without specific clinical indications for their use) decreased by approximately 60% (from 26.1% to 10.3%). The data indicate that the usage of calcium antagonists in GISSI studies has been strongly affected by the results of other large multicenter trials evaluating calcium antagonists. These agents are now prescribed in patients after AMI almost exclusively in the presence of specific indications such as systemic hypertension or angina.
Congestive heart failure is a lethal condition that affects an increasing number of patients. In recent years a great amount of data have accumulated on the pathophysiology and medical and surgical therapy of this condition. In spite of the advances in its management and the great number of patients affected, common errors are still made by internists and cardiologists in the use of drugs and therapeutic strategies. Digitalis has only recently been shown to affect hemodynamics, exercise capacity, and clinical symptoms, but the effects on survival still have to be demonstrated. Loop diuretics, eventually combined with thiazides and antialdosterone drugs in patients with clinical signs and symptoms of fluid retention, are the mainstays of therapy of congestive heart failure. In order to make diuretic therapy efficacious, moderate salt and water intake restriction is mandatory. Angiotensin-converting enzyme (ACE) inhibitors are now considered unavoidable drugs in the management of heart failure, and an attempt to reach the doses that have been shown to be efficacious for survival in the large trials has to be made in every patient with this condition. Other vasodilators, such as hydralazine and nitrates, which show a less pronounced effect on survival but more effective hemodynamic actions than ACE inhibitors, may be used to control mitral insufficiency or to improve hemodynamics in very sick patients. Hemodynamic instability refractory to increasing doses of vasodilators and diuretics is a severe condition that requires hospital admission to administer drugs parenterally. These patients are usually treated with the combination of catecholamines and phosphodiesterase inhibitors associated with intravenous diuretics until clinical stability is again achieved and oral therapy is resumed and restructured. The use of aggressive pharmacological therapy and phosphodiesterase inhibitors has reduced the need for assisted circulatory support in these patients. Beta-blockers have shown promising results when administered to patients with heart failure, although a definitive demonstration of their effects on survival is still lacking. Other additional measures that need to be considered in patients with end-stage congestive heart failure are the use of antiarrhythmic drugs and anticoagulation.
OBJECTIVE: To determine whether general practitioners (GP) who are readers of independent drug bulletins can be used as an international epidemiological observatory of the criteria adopted by "well informed" doctors in various countries in the management of mild hypertension. DESIGN: Questionnaire study of GPs' diagnostic criteria for mild hypertension, routine investigation and management of patients with this diagnosis. PARTICIPANTS: 206 GPs readers of independent drug bulletins in 7 countries, comprising 95 known systematic readers of a local bulletin and 111 randomly selected regular subscribers. MAIN OUTCOME MEASURES: Response rate to the questionnaire. Diagnostic criteria, routine investigations, and treatment used for patients with mild hypertension. RESULTS: The study required two months for planning and implementation. Four countries out of eleven had a response rate < or = 50% and were excluded; the frequency of responses from other countries was 69%. The average diastolic blood pressure (DBP) considered diagnostic of mild hypertension range from 94 mm Hg (lower threshold) to 106 (upper threshold). A minority (17%) of GPs routinely request the minimum recommended laboratory tests to assess patients. GPs routinely advise non-drug measures before starting a drug. Most would not start drug treatment in patients without other risk factors and a DBP below 100 mmHg. The top first choice drugs were diuretics and beta-adrenoceptor blockers. Half of the doctors were able to quote some published guide to the management of mild hypertension, and 18% cited a relevant trial. Attitudes in diagnosing and treating mild hypertension differed widely between GPs and countries. CONCLUSIONS: GP readers of drug bulletins can be used quickly and inexpensively to assess the extent to which recommended diagnostic and therapeutic practices are accepted by "well informed" doctors. The results suggest that attitudes in managing mild hypertension vary widely among GPs and countries and differ remarkably from the recommendations of published guidelines.
We propose a renal imaging agent, the 99mTc complex of the bidentate-N,S chelate N-(mercaptoacetyl)glycine (99mTc-2GAM), with the imaging characteristics of 99mTc-DMSA but a faster kidney uptake; chemical evidence supports the formulation of 99mTc-2GAM as [Tc(v)(O)(GAM)2]-. After biodistribution and toxicity studies in animals, 99mTc-2GAM was evaluated in five normal volunteers. 99mTc-2GAM is rapidly cleared from the blood (t1/2 = 9 min) and 50% of the ID is excreted in the urine in the first 2 h. Dynamic data show a rapid renal uptake that increases up to 1 h with no significant wash-out between 1 and 8 h. The uptake in each kidney ranges from 11.3% to 20.7% ID. Low, stable liver uptake is observed. No significant activity is detected in other organs. We showed no differences between 99mTc-2GAM and 99mTc-DMSA compared in three patients with unilateral kidney disease. We conclude that 99mTc-2GAM has good practical and dosimetric features for renal imaging.
With the current oncological emphasis on radical treatment allied to minimal invasiveness, choice of treatment relies on precise clinical staging. The corpora cavernosa of the penis represent a well defined anatomical structure distinct from the corpus spongiosum and the glans which are tightly connected to one another. In case of primary penile tumour the T.N.M. classification of the American Joint Committee on Cancer includes in the T2 stage both infiltration of the corpus spongiosum and of corpora cavernosa. Jackson's classification seems to be more pertinent as it limits to stage 1 cases involving the glans and corona and classifies as stage 2 cases limited to the corpora cavernosa. Partial penectomy can prove overly invasive, yet insufficiently radical, if the anatomical continuity of the spongious tissue is not considered. Carcinoma of the glandular corpus spongiosum without cavernosal involvement indicates glandulectomy with partial uretrectomy and apical cavernous-urethrostomy. Preserving the corpora cavernosa is an option of great relevance to the quality of life of the patient: erectile ability and stand-up micturition are not affected and the patient keeps complete sexual ability and orgasmic sensation. In case of scrotal or public involvement, emasculation with hemipelvectomy must be attempted; if indicated, it can be followed by radiotherapy. Perineo/abdominal reconstruction can be followed by urinary diversion with adjuvant chemotherapy. In selective cases neophallic reconstruction can be later attempted using the inferior abdominal rectum muscle.
The surgical treatment of the La Peyronie disease is the complet excision of the fibrom plaque followed by dermal skin grafts. This technique is applied for stabilised cases in which coït has become uneasy due to the deformation of the penis. A complete isolation of the vasculonervous dorsal pedicle guaranties a good erection. In 15 years this technique was applied in 400 cases followed during 2 years. In 7% of cases a recidive of the incurvation occurs. In 20% the erection was unsatisfactory.
Presence of bacteria in the sperm is often associated to a reduction of fertility in relationship with a decrease in number and motility of spermatozoa and with an augmentation of the abnormal spermatic cells. In the most severe cases, chronic and complicated phlogosis may lead to obstruction of seminal pathways with consequent azoospermia. Clinical features of seminal phlogosis are extremely variable both in acute and chronic evolutions. In every case the first diagnostical step is sperm count and seminal complete analysis which can give evidence of phlogistic alteration in quantity and quality of spermatic cells with a typical presence of an excess in white blood cells (leukospermia) as consequence of infection. The great variety in clinical and bacteriological aspects and the particular biological features of the organs involved, as the prostate, makes treatment a difficult problem to solve with particular regard to the choice of an effective antibiotic which pharmacokinetic has to result suitable for the microorganism as well as for the tissue of the infection site. All those efforts are indispensable to reduce the too frequent therapeutical failures in the management of seminal phlogistic pathology with complications of organic but also physiological relevancy for the patient and the partner too, such as azoospermia.
The endoscopic therapy has an elective role in the distal obstructive azoospermia for urogenital carrefour pathologies both organics and functional and differently in the resection and/or aspiration with sperm recovery forms. Resolutely attends to the symptomatology and positively to the fertility re-establishment, in front of a short sickness-rate. The Authors describe the different techniques with relative indications, results and complications. Instead medical therapy has a role in the obstructive above all post infection and post inflammatory lesions prevention. Furthermore propose to oneself the goal to improve the seminal quality by the improvement of the semen fertilization capacity and to reduce the affections symptomatology. Finally concurs with the sperm selection techniques to fertility potential wealth.
The authors report their experience of three cases of carcinoids of the gastroenteric tract which required emergency surgery. Two patients presented symptoms of acute appendicitis caused by appendicular carcinoid, whereas the third presented an occlusive syndrome due to ileal carcinoid.
BACKGROUND: Recent clinical trials have shown increased, rather than decreased, mortality in patients treated with antiarrhythmic drugs after acute myocardial infarction. OBJECTIVE: To determine whether these findings had an impact on prescription of antiarrhythmic drugs after acute myocardial infarction. METHODS: We retrospectively analyzed the class I and III antiarrhythmic prescription data of 38,072 patients with acute myocardial infarction enrolled in three large randomized clinical trials endorsed by a highly representative sample (about 75%) of Italian coronary care units during the last 10 years. The first study was conducted in 1984 to 1985; the second, in 1988 to 1989; the pilot for the third, in 1991; and the third, in 1991 to 1994. RESULTS: Total class I and III antiarrhythmic prescriptions after acute myocardial infarction was halved during the last decade, from 11.9% at discharge and 14.4% at follow-up in 1984 to 1985 to 5.8% and 5.8%, respectively, in 1991 to 1994. The trend was independent of the different distributions in the three studies of the patients' characteristics associated with antiarrhythmic use (ie, age > or = 70 years, anterior acute myocardial infarction, ventricular fibrillation during hospitalization, and Killip class > or = 2 at randomization). The same decreasing trend was observed for each antiarrhythmic drug. The drug most widely used was amiodarone, accounting for about half of the antiarrhythmic prescriptions, followed by mexiletine hydrochloride and propafenone hydrochloride; flecainide acetate was dropped from the prescription list after the publication of the Cardiac Arrhythmia Suppression Trial results. CONCLUSION: The negative results of the recent clinical trials on class I antiarrhythmic drug use after acute myocardial infarction have been rapidly transferred into routine clinical practice in Italy, since the proportion of patients who received class I and III antiarrhythmic drugs after acute myocardial infarction was halved from the early 1980s to the early 1990s.
PURPOSE: Several irradiation techniques are compared with regard to normal tissue complication probability and tumor control probability. METHODS AND MATERIALS: Normal tissue complication probability is calculated using a model based on the "critical element architecture." The probability of controlling an inhomogeneously irradiated tumor is calculated using a model that takes into account the heterogeneity of tumors (different radiosensitivity of clonogens within the tumor and the varying number of clonogens among patients with the same kind of tumor). The ratio of tumor control probability to normal tissue complication probability (therapeutic gain factor) at different levels of dose has been used as a score for the analysis of various irradiation techniques. RESULTS: The best irradiation techniques depends on many factors: irradiation genometry, irradiation field size, choice of the reference isodose, and it is dictated by the pathology of the lesions (noninfiltrating radioresistant tumors, infiltrating radioresistant tumors, noninfiltrating radiosensitive tumors, infiltrating radiosensitive tumors, arterovenous malformations). For the irradiation of the artero-venous malformations it is proposed to insert on the supplemental collimator a flattening filter to reduce the probability of inducing a poorly syncronized obliterative effect. CONCLUSION: We propose that for each kind of pathology to be treated radiosurgically, a proper irradiation strategy should be used.
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Estrogen receptors are expressed in several brain areas of various animal species, and steroid hormones exert physiologic and biochemical effects on the central nervous system. The aim of the present study was to evaluate in female adult rats, the suitability of 16 alpha [18F]fluoro-17 beta-estradiol ([18F]FES), a selective estrogen receptor ligand, for the in vivo assessment of brain estrogen receptors. This was considered to be a preliminary step in evaluating the potential usefulness of [18F]FES for studies of cerebral estrogen receptors with positron emission tomography (PET) in nonhuman primates and human subjects. We evaluated (a) the time course of the metabolic degradation of [18F]FES in blood; (b) the time course of distribution of the tracer in discrete cerebral areas; (c) the inhibitory effect of increasing doses of cold estradiol on cerebral [18F]FES uptake; and (d) the possibility of in vivo quantification of estrogen receptor binding parameters using both equilibrium and dynamic kinetic analyses. We quantified [18F]FES binding to estrogen receptors using both equilibrium and dynamic kinetic analyses. The results of this study indicate that [18F]FES is a suitable tracer for the measurement of estrogen receptors in the pituitary and hypothalamus, using either the equilibrium or the kinetic analysis. However, [18F]FES is inadequate for the in vivo investigation of estrogen binding sites in brain areas with low receptor density, such as the hippocampus.
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The present study was designed to assess the hemodynamic conditions, by means of impedance cardiography methods, and the relation existing between vascular reactivity to isometric stress (isometric handgrip test) and the day/night blood pressure variations, estimated by ABPM. Fifty unselected untreated non-obese EEH adult subjects (WHO class I) with a duration of disease not exceeding 3 years were classified as dippers or non-dippers according to commonly accepted criteria. Twenty three normotensive volunteers acted as controls. SBP, DBP, HR, CI and SVRI were assessed at rest and after IHG test. At rest dippers, non-dippers and controls showed comparable CI. SVRI were more enhanced in EEH than in controls and, although not significantly, in non-dippers than in dippers. During IHG all subjects showed a significant rise of SBP, DBP and HR; CI variations were of comparable size in all groups while SVRI increases were not. Non-dippers showed a significant SVRI rise after IHG in comparison with resting values. In dippers and in controls SVRI increment was insignificantly different in comparison with resting values. Non-dippers showed a closest correlation between BP and SVRI rise during IHG while dippers showed a less consistent association. In conclusion, our data suggest that in adults with short duration EEH the existence of non-dipper condition may be unrelated to myocardial hypertrophy. Blunted nocturnal BP fall is associated with vascular hyper-reactivity revealed by a bigger elevation of SVRI during IHG.(ABSTRACT TRUNCATED AT 250 WORDS)
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