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Biomedical subjects

L Poggi

Publications and source records attributed to L Poggi.

At least 55 records · Page 3Linked to original sources

Production of protein-associated DNA breaks by 8-methoxycaffeine, caffeine and 8-chlorocaffeine in isolated nuclei from L1210 cells: comparison with those produced by topoisomerase II inhibitors.

8-Methoxycaffeine (8-MOC) is a caffeine derivative, more potent than the parent compound, but very similar to caffeine in terms of induction of DNA single-strand breaks (SSBs), DNA double-strand breaks (DSBs) and DNA-protein crosslinks (DPCs). We have studied the capability of 8-MOC, caffeine and 8-chlorocaffeine (8-CC) of inducing SSBs, DSBs and DPCs, and we have compared 8-MOC with ellipticine, a typical inhibitor of DNA topoisomerase II. The DNA effects of 8-MOC appeared similar to those of ellipticine. In both cases SSBs, DSBs and DPCs were present in a similar ratio, and they were rapidly reversible after removal of the drug. The dose-response curve was bell-shaped for both compounds. In addition, 8-MOC, caffeine and 8-CC were capable of inhibiting DSBs induced by ellipticine. These results were obtained at the level of L1210 cell nuclei. In spite of these functional similarities, 8-MOC, caffeine and 8-CC were unable to stimulate the formation of a cleavable complex by purified L1210 topoisomerase II (p170 form) when SV40 DNA and human c-myc DNA were used as substrate. These methylated oxypurines could be active on a different form of topoisomerase II, or, alternatively, they could be active only in the natural chromatin 'milieu' within the nucleus.

Animals↗

[Antihypertensive treatments: drug efficacy effect and initial ambulatory blood pressure].

OBJECTIVE: we used initial whole day blood pressure (BP) level to evaluate antihypertensive therapy in different class of agents. DESIGN AND METHODS: The study was performed with 205 hypertensive patients. All patients had essential mild to moderate hypertension after single-blind placebo run in period. At the end of this period, and after 1 month of active treatment (3 class of agents: angiotensin converting enzyme inhibitors (ACEI) = 117, calcium channel blockers (CCB) = 52, beta-blockers (BB) = 36) casual blood pressure was performed and ambulatory BP was monitored during the whole day. At the start of the study, 91 of 205 patients had an ambulatory diastolic BP less than to 90 mmHg (group I: "normotensive patients") and 114 greater than or = 90 mmHg (group II: "hypertensive patients"). Clinical measurements and whole day BP monitoring are used to assess response to treatment for all patients and for the group I and II. RESULTS: Therapy decreased clinical BP by 19 +/- 15/11 +/- 9 mmHg and average whole day BP by 10 +/- 11/7 +/- 8 mmHg. In the 3 class of agents, there is no difference between group I and II at the start of study. ACEI treatment: In group I, decrease of average whole-day BP by 12/7 and by 11/8 mmHg in group II. In contrast for CCB treatment: 2/2 and 13/7 (p less than 0.001), for BB treatment 10/4 and 13/11. In the 3 class of agents, there is no difference in the clinical BP decreases between group I and II. CONCLUSION: Our data emphasize a significant discrepancy between clinical and ambulatory BP evaluation among patients displaying low ambulatory BP particularly with CCB treatment in contrast with ACEI treatment. In the low group, CCB decreased ambulatory BP less than ACEI did. These results suggest that there is a lesser chance of overtreating "normotensive" patients with CCB than there is with ACEI.

Ambulatory Care↗

[Ambulatory blood pressure, reproducibility, variability and change, placebo effect].

Blood pressure assessment by ambulatory recordings is a recent clinical method. What is the reproducibility and variability of the results and what is the circadian variation of blood pressure? How useful is the technique for evaluating therapeutic efficacy? Several groups have reported that the reproducibility is good within a group of patients but that this is not observed in case by case and measurement by measurement analysis; however, when the periods of observation are sufficiently long (several hours) the recordings are comparable. In clinical practice for an individual patient, it would seem better to compare the average daily pressure load, at rest and during activity, which is more reproducible than the hourly average of blood pressure. The circadian variation of blood pressure and short-term (within the hour) or long-term (24 hours) variability have been analysed in depth and although the ambulatory blood pressure shows the same circadian variation as invasive arterial measurement, it does not show instantaneous variability. The placebo effect is not marked when a large group of patients is studied. On the other hand, case by case analysis shows the persistance of this phenomenon in small numbers of cases and, in practice, these results make the maintenance of a placebo period in therapeutic trials a necessity. In conclusion, ambulatory blood pressure recording in daily medical practice enables the study of therapeutic variations in blood pressure over a 24 hour period. However, it does not yet enable satisfactory analysis of the variability of blood pressure.

Ambulatory Care↗

[Comparative study of enalapril, hydrochlorothiazide and their combination in the treatment of essential hypertension].

This was a randomized double-blind, multiclinic, parallel, three treatments group study to compare the safety and efficacy of a fixed-ratio combination of enalapril/hydrochlorothiazide (E/HCTZ: 20/12.5-40/25 N = 46) to enalapril (E = 20-40 mg, N = 49) and hydrochlorothiazide (HCTZ: 12.5-25 mg, N = 51) once daily, in the treatment of patients with moderate to severe essential hypertension (100 less than or equal to supine diastolic blood pressure less than or equal to 120 mmHg). A significant decrease of systolic and diastolic blood pressure was shown in the 3 subgroups of patients. The decrease of blood pressure was significantly greater in the E/HCTZ subgroup. After 8 weeks of treatment, the E/HCTZ group had the greatest proportion of normotensive patients (65.9 p. cent, DBP less than or equal to 90 mmHg) and of responders (81.8 p. cent, diastolic blood pressure decrease greater than 10 mmHg). The treatment groups did not differ significantly with respect to clinical adverse events. The study results document the well-known hyperuricemic effect of diuretics and also indicate that the combination of enalapril and HCTZ ameliorates this effects. In this study plasma potassium was slightly but not significantly decreased by HCTZ. The combination of enalapril and hydrochlorothiazide did not alter this parameter. The results support the conclusion that in the treatment of moderate to severe hypertension, the combination enalapril/HCTZ 20/12.5 to 40/25 mg, taken once daily, is more effective than either its components used alone. This combination is well tolerated, probably due to an adequate enalapril/HCTZ dosage ratio.

Adult↗

8-methoxycaffeine-induced protein-associated DNA breaks in isolated L1210 cell nuclei.

8-methoxycaffeine (8-MOC) is a caffeine derivative more potent than its parental compound in inducing chromosomal aberrations. 8-MOC has been postulated to produce chromosomal aberrations by DNA topoisomerase II inhibition. The effect of 8-MOC on nuclear DNA were studied by alkaline elution experiments and compared with those of Ellipticine and Adriamycin (ADR). Like Ellipticine and ADR, 8-MOC induced single strand breaks (SSBs), double strand breaks (DSBs), and DNA-protein cross-links (DPCs) in a bell-shaped manner with respect to drug concentration. As in the case of ADR and Ellipticine, 8-MOC induced equal SSB and DPC frequencies. These results could suggest that 8-MOC induces DNA breaks by interacting with DNA topoisomerase II or with a similar DNA metabolism enzyme.

Animals↗

Effect of recombinant human TNF on human ovarian cancer cell lines.

Ovarian cancer is the second most common gynecologic malignancy. Standard therapeutic approaches to this disease, surgery followed by chemotherapy, have produced response rates of up to 80%. However, the five-year survival rate remains around 30%. Recently, Tumor Necrosis Factor (TNF) has received attention as either an alternative or an associated agent for chemotherapy of ovarian cancer. TNF is known to have direct cytotoxic and cytostatic effects on a variety of transformed cell lines "in vitro". Furthermore, TNF is known to enhance significantly the "in vitro" effects of a class of chemotherapeutic agents, specifically those targeted at DNA topoisomerase II. In this work we have investigated TNF-induced cytotoxicity in four established human epithelial ovarian cancer cell lines: A-2774; SV-626; SKOV-3 and Pa-1. TNF mediated cytotoxic activity was observed in a range of concentrations between 1 U/ml and 10-3 U/ml. A-2774 and SV-626 were the two most sensitive lines, especially when exposed to high concentrations of TNF.

Cell Survival↗

[Arterial pressure--self measurement. Recommendations. French Society for Arterial Hypertension--the Measurement Group].

Self-measurement of blood pressure has become widespread in recent years. It may be defined as the measurement of arterial pressure by a conscious and free-willed subject. Self-measurement must remain a medical procedure, which means that doctors should be able to advise their patients (a) on the type of apparatus they should purchase and get validated at regular intervals; (b) on the method of using the apparatus in practice, and (c) on the circumstances, conditions and numbers of measurements to be performed. Doctors must remain responsible for the interpretation of the results obtained and for the diagnostic, pronostic an therapeutic applications of the method. Self-measurement of blood pressure naturally has advantages and disadvantages, but it must be noted that it may offer an alternative to hospitalization or to ambulatory arterial pressure measurement, avoid excessive or defective therapies and improve the patient's compliance with his treatment.

Blood Pressure Determination↗

Esophageal achalasia. Diagnostic and therapeutic implications.

Over an 11-year period, 15 patients underwent surgery for achalasia (Heller's operation with added antireflux procedure). Thereafter due to the use of manometry 25 other achalasic patients were diagnosed and 17 of them underwent the same surgical procedure. Manometry was done by means of a triple-lumen catheter as described by Arndorfer. Surgical results in the first group were good in 80% and moderate in 20% with no recurrence or organic complications due to acid reflux, while in the second group good results were 95%. In 16 cases of the second group, diagnosis was based on manometric recordings, since the radiological findings were lacking. Early diagnosis enabled to operate on selected patients according to the motor findings of the esophageal body. Follow-up by manometry revealed in some cases an increase in post-deglutitory motor activity and in two cases a return of a coordinated peristalsis. Clinical and functional results are discussed and the role of manometric studies is stressed in order to improve the knowledge of the pathophysiology of functional diseases of the esophagus.

Adult↗

[Validity of ano-rectal manometry in the diagnosis of cathartic colon as a cause of chronic pseudo-obstruction of the colon. Considerations on a case].

Cathartic colon is a rare pathology which hits old people and is radiologically characterized by dolichocolon and megarectum. It is nearly sure that the unusual length of the whole colon might be the first source of the cathartic disease. Rectal ampulla dilatation (megarectum) is due to the extended use of laxatives which induce changes in smooth muscle and in the myenteric nervous plexus. The anatomo-pathological changes of the rectum have been proved so far by histological examination of local and deep biopsy; now, in our opinion, they can be shown by manometry. The authors emphasize the possibility that cathartic colon might give episodes of diarrhoea and also recurrent bowel obstructions limited to the colon and so-called "chronic pseudo-obstruction" of the colon. They describe a case of this rare pathology admitted and treated in their ward. Gastric and esophageal motility in the patient was normal as was the motility of the upper rectum. Therefore they think that changes resulted from extended use of cathartics. In both cases patients show low manometric pressure, disordered peristalsis and in particular lack of internal anal sphincter relaxation in response to high balloon distension. As the occlusive status developed in an old patient (the patient was 81 years old), the authors think that the functional disorders were absent at birth. Cathartic colon is, in the authors experience, a cause of chronic pseudo-obstruction of the colon. Rectal manometry makes it possible to avoid surgical treatment. The therapy of pseudo-occlusion, if correctly diagnosed, consists in endoscopic intubation and decompression of the colon.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Non-invasive ambulatory blood pressure measurement over 24 hours: effects of labetalol on the rise of blood pressure in the early morning].

Three french specialist centers have included 19 hypertensive patients in an open cooperative study of the effect of labetalol (L = 200 to 400 mg b.i.d.) on the 24 hour blood pressure (24 h - B.P.) recording by a non invasive method (Spacelabs - Squibb Medical Systems), with a particular assessment of the early morning rise of BP. Each patient was subjected to 2 assessments at the end of a 14 days' placebo period and of a 28 days' treatment period. At the end of the study, the systolic (SBP) and diastolic (DBP). B.P. were significantly decreased at rest (p less than 0.001) and on the 24 hours recording (p less than 0.001). The reduction of B.P. was also significant on day period from 7 a.m. to 22 p.m. (p less than 0.001) and night period from 22 a.m. to 7 a.m. (p less than 0.05) as well as on the early morning period, 3 hours before and after waking (p less than 0.001). The heart rate was significantly reduced during the day (p less than 0.05) and was not on the night. The slope of the early morning rise of B.P. was marked after placebo and significantly decreased after labetalol with a reduction of 52% for SBP and 49% for DBP (p less than 0.001). These results show that labetalol has an antihypertensive effect over 24 hours with a marked effect on the early morning rise of B.P.

Adult↗

[Manometric findings on esophageal motility in patients with reflux esophagitis].

The aim of the study was to investigate the incidence of the acid reflux and its relationship to the oesophageal motility and to clinic symptoms. Recording of oesophageal manometry under basal and stimulating conditions obtained from 30 patients GERD and 10 healthy controls were assessed. Manometric results were analyzed for the occurrence of failed primary peristalsis, for the occurrence of peristaltic dysfunctions or for hypotensive LES pressure. Motor abnormalities found in the body of the oesophagus during simulated oesophageal reflux were described. The AA. found that there is not a sure correlation between the occurrence of peristaltic dysfunctions and hypotensive LES such as was not possible to find a direct relationship between peristaltic disorders and oesophagitis degree or symptoms.

Adult↗

Comparison of once and twice daily administration of captopril plus hydrochlorothiazide on 24 h blood pressure levels.

The anti-hypertensive effect of captopril 50 mg plus hydrochlorothiazide 25 mg, given once or twice daily, was investigated by 24 h monitoring in hypertensive patients in a controlled, randomized, double-blind, cross-over trial. Ten patients with blood pressure (BP) greater than 160 and/or 95 mm Hg after a 15 day placebo period, were randomly assigned to one of two treatments, in which they either received the combination once daily in the first month, twice daily in the second and once daily in the third (Treatment Group A) or twice daily in the first month, once daily in the second month and twice daily in the third month (Treatment Group B). The anti-hypertensive effect of the drug combination was assessed by 24 h monitoring using a Dinamap 845 to establish mean BP levels and circadian curves. After 1 month the twice daily administration was more effective than the once daily, but after 2 months, and throughout the third month, there was no difference in the anti-hypertensive efficacy of the combination given either once or twice daily.

Blood Pressure↗

Asanguineous isolated hyperthermic in vivo perfusion of the liver in the rat.

An experimental study was conducted in the rat to evaluate the sensitivity of the liver to hyperthermia and ischemia. A 15-min asanguineous isolated hyperthermic in vivo perfusion of the liver was done in rats with a normal liver and in rats with an hepatocarcinoma induced by chronic 3'-diethylaminoazobenzene intoxication. The perfusion was made using various ranges of temperature of the perfusate. In normal rats, the in vivo perfusion was well tolerated as long as the mean intrahepatic temperature remained under 38 degrees C. Postoperative evolution of serum transaminase level was similar whatever the temperature of the perfusate. Histological lesions of the hepatic parenchyma were as severe as the temperature of the perfusate was elevated. In rats with tumors, the mortality rate was elevated in the animals with large tumors. A moderate decrease in the serum alpha-fetoprotein level was observed during the first days after liver perfusion. In all cases, death occurred apparently as a direct consequence of liver injury. This study defines the sensitivity of the normal or neoplastic rat liver to hyperthermia and ischemia using a model of isolated in vivo perfusion of the liver. It provides a basis for further investigations on the effect of hyperthermia on experimental liver tumors.

Alanine Transaminase↗

[Antihypertensive therapeutic effect. Comparison of their evaluation using clinical and ambulatory measurements of arterial pressure. Preliminary study].

The aim of this preliminary report is to compare the evaluation of the antihypertensive drug effect, during a controlled trial, using casual measurements and 24 hr B.P. monitoring. 20 patients (16 males, 4 females 55 +/- 10 years old) with primary hypertension (WHO stage I or II) were included with a diastolic blood pressure greater than or equal to 100 mmHg (mean blood pressure from three clinical readings). Casual B.P. and B.P. monitoring (Spacelabs - 4 measurements per hour during a 24 hr period) were established before and after the end of the placebo run in period (one placebo tablet given once daily at 8 h-8 h 30 a.m. for 15 days). Overall sample data: The clinical B.P. decrease (167 +/- 16-109 +/- 7 before and 147 +/- 17-97 +/- 11 after treatment) is higher that the ambulatory B.P. decrease (148 +/- 15-101 +/- 8 before and 138 +/- 21-94 +/- 14 after treatment). Individual patient data: A clinical B.P. decrease (of at least 10 mmHg) was found in 17 patients for systolic B.P. and in 15 patients for diastolic B.P. A significant ambulatory B. P. drop decrease (p less than 0.05) was found in 11 patients for 24 hr systolic and diastolic B.P. The clinical and ambulatory responses to the treatment are in line in 14 patients, but differ in 3 instances. There is a little correlation (for the diastolic B.P.) and no correlation (for the systolic B.P.) between the clinical and the ambulatory B.P. decreases after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Study of the placebo effect in using the non-invasive ambulatory measurement of blood pressure].

The aim of this study is to evaluate the antihypertensive effect of placebo assessed by 24 hr non invasive blood pressure monitoring. 20 patients (16 males, 4 females, 55 +/- 10 years old) with primary hypertension (WHO stage I or II) were included with a diastolic blood pressure greater than or equal to 100 mmHg (mean blood pressure from three clinical readings). Casual blood pressure and blood pressure monitoring (Spacelabs - 4 measurements per hour during a 24 hr period) were established before and at the end of the placebo run in period (one placebo tablet given once daily at 8 h-8 h 30 a.m. for 15 days). Overall sample data: There was no antihypertensive effect of the placebo with casual BP (167 +/- 16-109 +/- 6 mmHg before and 167 +/- 16-109 +/- 7 mmHg after placebo) and with 24 hr B.P. monitoring (142 +/- 14-96 +/- 8 mmHg before and 141 +/- 14-96 +/- 8 mmHg after placebo). The circadian curves were similar. Individual patient data: A clinical placebo effect (B.P. decrease of at least 10 mmHg) was found in 5 patients for the systolic B.P. and in 2 for diastolic B.P. A significant ambulatory placebo effect (p less than 0.05) was found in 5 patients for the 24 hr systolic B.P. and in 4 patients for the 24 hr diastolic B.P. However, patients with clinical placebo effect were not the same as those with ambulatory placebo effect. There was no correlation between the clinical and the ambulatory response to placebo treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Has the prognosis of recent myocardial infarction changed?].

In this retrospective study changes in the prognosis of recent myocardial infarction were evaluated by comparing 731 patients hospitalized in the 1970-1974 period (group I) with 755 patients hospitalized in the 1984-1986 period (group II). The possible factors responsible for the changes observed were investigated. A 34 percent decrease in hospital mortality was recorded (19.2% in group I versus 12.6% in group II; P less than 0.001). The decrease was present irrespective of the patients' sexes and ages; it was more pronounced in patients under 65 (-42%) and in elderly women (-43%). Compared with group I patients, group II patients showed a significant decrease in cardiogenic shock (P less than 0.02), atrial fibrillation (P less than 0.05) and, chiefly, atrioventricular block (P less than 0.001). The improvement in prognosis cannot be ascribed to a change of population since both groups were matched in male to female ratio, age distribution and presence of the main risk factors. Three factors may have contributed to a better prognosis: (1) more rapid admission to hospital; the proportion of patients admitted within 6 hours of the initial symptoms rose from 37.5% in group I to 49.8% in group II (P less than 0.001); (2) modification of the conventional treatment, with a reduced prescription of digitalis and a less frequent recourse to temporary electrical pacing; (3) introduction of new treatments aimed at limiting the size of the necrotic area; these include thrombolytic agents which were administered in 19.2% of patients under 65 and may well have played the principal role in the improvement of outcome.

Adult↗