Biomedical subjects
Publications and source records attributed to F Colombo.
In 3858 ambulatory elderly people (age greater than or equal to 65 years) prevalence of hypertension was 67.8%. The hypertensive status was unknown to both the doctor and the patient in 21.4% of cases. More than 90% of known hypertensives were treated, but hypertension could be considered as controlled in less than 30% of them.
Hexakis (methoxyisobutilisonitrile) technetium(I), 99mTc-MIBI, has been proposed for myocardial perfusion studies. We have evaluated the biodistribution of this new agent in normal volunteers at rest and after stress. The biodistribution of 99mTc-MIBI is characterized by rapid blood clearance and a consequently early myocardial uptake. The initial intense hepatic activity is cleared into the gallbladder at 1 h after injection, and the best target to non target ratio is observed at 60-90 min after injection. Absorbed radiation dose calculations show that the thyroid is the critical target organ (230 mRad/mCi at rest), presumably because of 99mTc-pertechnetate generated in vivo. Our results indicate that 99mTc-MIBI is a promising tracer for myocardial perfusion imaging.
The in vitro effects exerted by tetroxoprim and sulfadiazine on T lymphocyte proliferation were evaluated at drug concentrations equal to and twice the plasmatic peak level of each drug. The two drugs did not exert any significant effect on spontaneous and mitogen (PHA) or monoclonal antibody (MAb anti-CD3) induced T lymphocyte proliferation at the studied concentrations, both when tested separately and combined. In addition the two compounds did not significantly interfere in gamma-interferon (IFN-gamma) production.
Fourteen patients with nonoperable low-grade astrocytomas were treated with unconventionally fractionated stereotactic radiation therapy. The target volume was defined with computed tomography (CT) performed under stereotactic conditions. The treatment was carried out with a technique producing multiple noncoplanar arc irradiation, with the center of the target volume placed at the isocenter of the linear accelerator. A total dose of 16-50 Gy was administered in either one fraction or two fractions 8 days apart. The concentration of dose within the target volume allowed reduction of dose absorbed by adjacent critical structures of the intact brain. Patients were followed up for 11-48 months. Twelve of 14 patients had a partial or complete response to treatment, as demonstrated by CT. Stereotactic radiation therapy appears to be effective in the control of small radioresistant cerebral neoplasms, without damaging surrounding healthy tissues.
A technique for linear accelerator radiosurgery has been used in clinical practice since 1982. The technique is based on multiple intersecting arc irradiations focused on a stereotactic target. From November 1984 to October 1988, 97 patients with cerebral arteriovenous malformations have been treated. Seventy-nine patients suffered one or more than one hemorrhage. Four patients had progressive neurological symptoms. In 14 patients, epilepsy was the principal complaint. Stereotactic localization was performed by stereotactic angiography. Lesion dimensions varied from 4 to 40 mm in diameter. Doses from 18.7 to 40 Gy were delivered in one or two sessions. Mean follow-up is 17.1 months (from 1 to 49). Four instances of minor rebleeding were observed after treatment; 3 patients complained of transient neurological deterioration. Of 56 patients who were followed longer than 1 year, 50 underwent 12-month follow-up angiography. In 26 patients complete obliteration of the malformation was demonstrated (52%), in 12 patients subtotal obliteration was obtained (24%), in 11 patients the obliteration was evident but not significant (22%), and in 1 patient the AVM was unchanged. Other angiographic features in incompletely obliterated cases were a significant reduction of flow velocity through the malformation together with a reduction in diameter of both feeding arteries and draining veins.
In order to assess the antihypertensive care received by the elderly, where clear therapeutic guidelines are lacking, a population of 3,858 aged over 64 years was studied. Data were derived from a large Italian 'Study on Blood Pressure in the Elderly', carried out in general practice. Over 90% of the 2,059 known hypertensive patients were receiving drug treatment, with no age or sex-related differences. A single drug was prescribed to 50.2% of treated patients; only 5.5% were receiving three or more drugs. Diuretics and older sympatholytic agents were by far the most frequently prescribed categories, with four drugs (hydrochlorothiazide, amiloride, methyldopa and chlorthalidone) accounting for over 50% of all prescriptions. Low-dosage treatment schedules were frequently used, often associated with less-often-than-daily drug administration. Our study shows that physicians' attitudes to the treatment of arterial hypertension in the elderly are fairly uniform, with treatment of all subjects but with low drug dosages.
The aim of our investigation was to assess blood pressure and heart rate variations in 20 essential hypertensive male in-patients (WHO class I and II) and in 20 normotensive healthy volunteers submitted to three provocation tests: isometric handgrip (IHG), bicycle ergometric exercise (BEE) and tyramine infusion (TI) given as i.v. boluses alternating with saline in a single-blind fashion. According to our data IHG induced a comparable rise of systolic BP, diastolic BP and heart rate both in hypertensive and normotensive subjects. BEE, compared with IHG, caused a more significant (P less than 0.01) rise in SBP and heart rate in both groups. By contrast, DBP during BEE was significantly increased in hypertensive (P less than 0.01), but slightly decreased in normotensive subjects (P = NS). TI caused a dose dependent SBP rise in both groups studied, while DBP and HR were unaffected. BP elevation was, however, more marked in hypertensive subjects. Confirming this finding significantly lower tyramine doses were required to produce the same SBP increase in hypertensives than in the normotensive volunteers. In short, SBP rise during TI and DBP rise during BEE may be the markers of an enhanced cardiovascular reactivity of hypertensive subjects. Our study suggests that BP reactivity to stress may be different according to the laboratory stress employed and also that BEE and TI are more useful than IHG for the assessment of an enhanced cardiovascular response to stress in hypertensive subjects.
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254 patients affected by intracranial lesions underwent stereotactic biopsy in our department from 1978 to 1986. Target localization was achieved by CT. Multiple biopsy sampling was performed by cup microforceps or sliding cannula. Operative mortality was limited to 2 cases. Definitive tumour diagnosis including type and approximate grading was obtained in 211 (83%) patients. Diagnostic failures have been investigated from the neuroradiological point of view. Failure rate is low in solid tumours with CT homogeneous appearance and clear-cut borders, gradually increases in non homogeneous tumours, necrotic haemorrhagic or cystic, and is high in non classifiable lesions, generally hypodense at CT, with indefinite borders. In the authors opinion the variability of diagnostic retrieval in different types of lesions must be taken into account when proposing stereotactic biopsy.
The effect beta-adrenoceptor blockade on the pressor response to tyramine has been investigated in 6 healthy volunteers, each submitted to an i.v. tyramine pressor test before and after 7 days of propranolol 40 mg b.d. or indenolol 60 mg o.d. Tyramine was given as i.v. boluses of 1-6 mg, alternating with saline, in a randomized, single blind fashion. Prior to treatment tyramine caused a temporary, dose-dependent increase in systolic and diastolic blood pressure, whilst the heart rate remained unaffected. Both propranolol and indenolol reduced the pressor response to tyramine, as shown by a significant increase in ED15, i.e. the dose of tyramine required to increase systolic blood pressure by 15%.
The aim of this paper is to present the physical and dosimetrical features of the stereotaxic radiosurgical method already published by the authors. This method concentrates the dose into the stereotaxic target volume, placed at the isocenter of a 4 MV X-ray beam. Computer calculations showed that: 9-17 arcs provide almost spherical dose distributions; the optimal photon beam quality is about 4-6 MV. The angle between adjacent rotation planes is 20-40 degrees and the arcs are 100-160 degrees wide. In this way the dose to healthy tissue is minimized. The dose distribution was experimentally verified both by ionometric and photodensitometric methods. The procedure for dose calculation at isocenter of fields as small as required by the radiotherapist, has been investigated.
A number of symptoms that appear to be associated with high blood pressure (headache, dizziness, epistaxis, tinnitus, weakness, drowsiness), and are usually regarded as secondary to hypertension or to antihypertensive drug therapy, were studied in 3858 elderly patients, 67.8% of whom were hypertensive. Of the hypertensive patients, 71.2% were under treatment. Headaches and dizziness were significantly more prevalent in the hypertensive than in the normotensive subjects (32.5 versus 27.4% and 41.5 versus 35.3%, respectively; P less than 0.05) and in treated compared with untreated hypertensives (33.3 versus 29.4% and 43.3 versus 37.1%; P less than 0.05). These differences disappeared after statistical correction for 'awareness of hypertension'. In multiple logistic analysis, female sex, age and awareness of hypertension were significantly associated with a higher prevalence of symptoms, whereas hypertension and antihypertensive treatment were not. We conclude that the presence of these symptoms does not constitute a reliable criterion for starting antihypertensive treatment or judging its efficacy.
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A study of blood pressure control in elderly outpatients was carried out with the participation of 444 Italian general practitioners. Of 4096 patients aged 65 years or over who were considered for recruitment, 3959 (96.7%) fulfilled all the criteria of admission and were followed up for 12 months. The findings regarding one of the aims of the study--that is, to assess the feasibility of a large scale trial in general practice--are reported. Most (87%) of the doctors completed the study. Their adherence to the protocol was highly satisfactory, leading to an acceptable quality of work. Patients' compliance was also good; 98.6% (3898) of the patients who had fulfilled the admission criteria agreed to participate in the study, and only 4% (158) dropped out. Both of these observations support the feasibility of carrying out prospective studies in general practice. The creation of networks of general practitioners who are prepared to carry out research in their practices would allow treatment and preventive measures to be studied simply and at low cost in the appropriate setting.
A new method for external stereotactic focal irradiation of three-dimensional irregular target volumes is proposed. In this method the target is irradiated by a linear accelerator set in various angular positions around the isocenter. During the irradiation the target is translated in a direction perpendicular to the beam. By controlling the velocity of the translation it is possible to modify the configuration of therapeutic isodoses so as to make them follow the borders of the target.
Behavioral and pharmacological evidences suggest that dopaminergic mechanisms in striatum might be counteracted by adenosine or potentiated by its pharmacological antagonists methylxanthines. To test whether adenosine modulation of the dopaminergic function could be, at least in part, due to an interaction at the level of the adenylate cyclase complex, we studied the effects of the adenosine analog R-Phenyl-isopropil-adenosine (R-PIA) on basal and dopamine-sensitive adenylate cyclase in rat striatum. R-PIA, which interacts with both adenosine A1-inhibitory and A2-stimulatory receptors, dose-dependently inhibited the stimulation induced by dopamine, and seemed to utilize the same pool of enzyme linked to dopaminergic D1 receptors. Two experimental approaches leading to supersensitivity of striatal dopaminergic receptors, (i.e., 6-hydroxy-dopamine injection in substantia nigra and reserpine administration) also induced upregulation of adenosine-dependent adenylate cyclase in striatum, and altered R-PIA modulation of dopamine-sensitive adenylate cyclase. Conversely, after subchronic treatment with neuroleptics such as haloperidol or sulpiride, upregulation of 3H-Spiroperidol binding in striatum was not associated with changes of R-PIA dependent adenylate cyclase in this area. It is concluded that adenosine might modulate post-synaptic responses to dopamine via adenosine receptors which functionally interact with dopaminergic D1 receptors in striatum.
Forty-five patients affected by cerebral arteriovenous malformations not suitable to open surgery have been treated by a radiosurgical technique employing a linear accelerator. One-year follow-up angiography is available for 10 cases. Therapeutic effect of focalized irradiation is presented.