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Biomedical subjects

F Ries

Publications and source records attributed to F Ries.

At least 19 recordsLinked to original sources
PubMed1992

Genetic aspects of multidrug resistance.

Gene amplification is responsible both for dihydrofolate reductase induced methotrexate resistance, and for the P-glycoprotein encoding multigene family induced multidrug resistance. The 6 pairs of hydrophobic regions of the P-glycoprotein fold up in a snake-like structure through the lipidic layers of the cell membrane. Other detoxification mechanisms include the glutathione S-transferase 'pi', but without gene amplification.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

The genetic basis of multidrug resistance.

Cellular multidrug resistance, a common side-effect of anticancer chemotherapy frequently leading to failure of the treatment, has been characterized as an acquired resistance to several antimitotic drugs simultaneously. Multidrug resistance could mainly be attributed to the overexpression of the P-170 glycoprotein, considered as a drug-efflux pump encoded by the mdr 1 gene. Overexpression of this protein can be induced either by an accidental amplification or activation or both of the mdr 1 gene. Recent investigations focused on these mechanisms, aiming at a better understanding of the appearance of multidrug resistance during a chemotherapy. P-glycoprotein mediated drug resistance, however, is only one, albeit quite an important detoxification pathway, and some observations revealed genetic interactions with other systems. On the basis of this new knowledge, the development of novel therapeutic strategies to circumvent this clinical side-effect of cancer treatment has already begun.

Antineoplastic Agents↗
PubMed1992

[Total intravenous anesthesia using propofol and alfentanil as compared to combined inhalation anesthesia reduces the flow velocity in the middle cerebral artery. A Doppler sonographic study].

Anesthesia for craniotomies should guarantee hemodynamic stability, preservation of cerebral autoregulation, and rapid postoperative recovery of consciousness. Increases in intracranial pressure (ICP) and postoperative respiratory depression should be avoided. Combined anesthesia (KA) with N2O and volatile anesthetics may increase cerebral blood flow (CBF), ICP, and cerebral oxygen consumption. According to recent studies, total intravenous anesthesia (TIVA) with propofol and alfentanil seems to best fulfill the requirements. Using transcranial Doppler sonography (TCD) (TC2-64, EME), we studied the influence of TIVA and KA under normo- and hyperventilation on the blood flow velocity (BFV) and pulsatility of the middle cerebral artery (MCA). METHODS. Two groups of 10 patients each undergoing craniotomy were investigated. Systolic and mean BFV, pulsatility index, mean arterial blood pressure, heart rate, and arterial CO2 tension were measured at four time intervals: (1) preoperatively; (2) 15 min after anesthesia induction under normoventilation, preoperatively; (3) 25 min after anesthesia induction under hyperventilation, preoperatively; and (4) 6 h postoperatively. The patients were premedicated with flunitrazepam 1 mg PO. TIVA was induced with 60 mg propofol, 1 mg alfentanil, and 6 mg vecuronium; simultaneously infusions of propofol (15 mg/min) and alfentanil (0.3 mg/min) were started and were maintained until the dura was completely opened. The infusion rates were then reduced to 6 mg/min propofol until skin suturing and 0.1 mg/min alfentanil until dural suturing was completed. Patients were ventilated with O2/air (fiO2 = 0.5). In the KA group anesthesia was induced with 4-6 mg/kg thiopental, 0.15 mg fentanyl, and 6 mg vecuronium and maintained with boluses of fentanyl, N2O (fiO2 = 0.5), and isoflurane (1.3 MAC). The time course is illustrated in Figs. 1 and 2 and the results are shown in Tables 1 and 2. They were tested using a one-factor analysis of variance and the Kruskal-Wallis range test. RESULTS. There was a significant decrease in systolic and mean BFV combined with an increase in pulsatility index after induction of TIVA, while KA induction effected no significant change in cerebral hemodynamics. The subsequent hyperventilation caused a similar decrease in mean BFV and increase in pulsatility index in both groups. CONCLUSION. Using the assumption that the diameter of the MCA is nearly constant, the reduction in BFV associated with an increase in pulsatility during TIVA is explainable as a decrease in CBF. By having a comparable influence on hemodynamics, the reduction in CBF with increase in cerebral vascular resistance seems to make TIVA the more advantageous anesthesia technique for patients with reduced intracranial compliance.

Adult↗
PubMed1992

[Is there an unusual incidence of the manifestation of intracranial angiomas in pregnancy? Risk assessment based on 17,733 patients over 10 years].

From 1979-1988, 134 inpatients (m:f = 80:54) were treated because of an intracranial angioma (AVM). The male/female ratio was 3/2 in general as well as during the "reproductive age" (15-45 yrs). In 6 patients (20-27 yrs; grav 2/para 1: n = 3; grav 1/para 0: n = 3) the AVM became symptomatic during pregnancy (n = 4: 23-33 gestational week) or at birth (n = 2). In the group of the presently non-pregnant women (n = 40) 47 uncomplicated deliveries had occurred years before. We conclude that the available data neither allow us to reject nor to confirm the hypothesis that pregnancy and/or delivery influence the manifestation of cerebral AVMs. The reasons for this dilemma of epidemiology are discussed.

Adolescent↗
PubMed1991

Use of intravenous immunoglobulin in chronic lymphocytic leukemia. A brief review.

Chronic lymphocytic leukemia (CLL) is a disorder with multiple defects leading to an increased susceptibility to infection. Hypogammaglobulinemia is present in about 20% to 70% of patients with CLL. Intravenous immunoglobulin (IVIG) supplementation (400 mg/kg body weight every 3 weeks) prevented bacterial infections in these patients. An ongoing study is being conducted to compare doses of 250 mg/kg/mo with those of 500 mg/kg/mo in 36 patients included so far. As of this writing, the rate of infection in the two treatment groups was not significantly different, and no substantial loss of protection against bacterial infection was found in the lower-dose group. It seems likely that the lower dose is almost as effective as the standard therapy. If this is so, cost savings would be substantial.

Humans↗
PubMed1991

Barbiturates in severe head injuries?

Possible mechanisms for the therapeutic effects of barbituric acid derivatives in severe head injuries have been discussed for half a century. In the following, a survey of the literature, and a discussion of three controlled clinical studies available until now is presented. A proven effect in terms of a beneficial long-term outcome for all injured patients has not been established. On the other hand there might be a subgroup of patients with an intact CO2 reactivity of the brain vessels who may profit from barbiturates administered after head trauma.

Barbiturates↗
PubMed1991

Treatment of advanced and refractory breast cancer with doxorubicin, vincristine and continuous infusion of verapamil. A phase I-II clinical trial.

Cancer cell resistance to several cytotoxic drugs, including doxorubicin and vincristine can be reduced in vitro by verapamil; this drug works at least in part by inhibitive competition for the multiple-drug resistance efflux-pump P-glycoprotein-170. To evaluate the clinical potential of this experimental concept we combined verapamil in continuous infusion with adriamycin and vincristine in the treatment of patients with advanced and anthracycline-refractory breast cancer. Sixteen patients were included and 55 treatment courses were given at different dose levels of chemotherapy; verapamil was given by continuous infusion of 0.003 mg kg-1 min-1 for 48 h. Overall, cardiac toxicity was low but a potentiation of neurotoxicity and hematotoxicity was observed. The objective response rate was 21% (3 partial responses in 16 patients) and the median survival was 6 months; these results are comparable to those of other second line treatment studies, using drugs not supposed to be cross-resistant.

Adult↗
PubMed1991

Prion diseases in man.

Human spongiform encephalopathies (HSE) are uncommon neurodegenerative diseases of unknown etiology. Whilst numerous observations provide arguments for an infectious disorder mediated by an unconventional agent of the so-called prion-type, the recent discovery of predisposing allelic variants suggests that HSE might be considered as genetically linked diseases.

Animals↗
PubMed1991

[Cavernous angiomas in the differential diagnosis of cerebrovascular malformations].

Cavernous angiomas, although rare, represent a clinical and a neuroradiological challenge in the differential diagnosis of cerebrovascular malformations. We report about three cases with a total of seven cavernous angiomas. Clinical features include intracerebral hemorrhage, epileptic seizures and focal neurological signs. Diagnosis is based on typical findings in MRI in combination with an angiography presenting a normal vascular situation or an avascular mass lesion, whereas CT-scan shows nonspecific features. Surgical removal is generally recommended, but could not be done in our cases. A histological verification of a clinically typical diagnosis is not mandatory. Indication for proton beam irradiation still has to be discussed. A definite therapeutical approach will have to consider the natural history in a larger number of cases.

Adult↗
PubMed1991

Correlation of regional cerebral blood flow and blood flow velocity in normal volunteers and patients with cerebro-vascular disease.

Transcranial Doppler sonography and measurement of regional cerebral blood flow using the Xenon133-inhalation technique have been used simultaneously in 10 normal volunteers and 13 patients with acute-onset cerebrovascular disorders during normocapnia and during hyperventilatory hypocapnia. Hypocapnia led to a reduction of both blood flow and blood velocity in the territory of the middle cerebral artery. However, correlation was poor in most cases with respect: 1) to hemispheric blood flow and flow velocity over the middle cerebral artery (BFV), 2) cerebral blood flow (CBF) over the middle cerebral artery (MCA) and BFV and 3) percentage changes of CBF over the MCA and BFV during hypocapnia. In normals correlation usually was better than in patients with cerebrovascular disorders. It was concluded that measurement of BFV over the MCA using transcranial Doppler sonography does not reflect either cerebral tissue perfusion or changes of tissue perfusion induced by alteration of CO2-content in the arterial blood.

Adult↗
PubMed1990

Cisplatin combined with carboplatin: a new way of intensification of platinum dose in the treatment of advanced ovarian cancer. Belgian Study Group for Ovarian Carcinoma.

We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.

Adult↗
PubMed1990

A comparison of ondansetron with metoclopramide in the prophylaxis of chemotherapy-induced nausea and vomiting: a randomized, double-blind study. International Emesis Study Group.

The efficacy of ondansetron was compared with metoclopramide in the prophylaxis of nausea and vomiting induced by cyclophosphamide greater than or equal to 500 mg/m2 in combination with doxorubicin greater than or equal to 40 mg/m2 or epirubicin greater than or equal to 40 mg/m2. complete anti-emetic protection in the 24 h following chemotherapy was achieved in 26 of 40 (65%) patients treated with ondansetron compared with 17 of 42 (41%) patients treated with metoclopramide. Severe nausea was present in 3% of patients in the ondansetron group and 31% in the metoclopramide group. A worst day analysis of control of emesis and nausea on days 2 and 3 following chemotherapy also demonstrated ondansetron to be more effective than metoclopramide. Both treatments were well tolerated. Ondansetron is more effective as an anti-emetic than metoclopramide in this type of cytostatic therapy.

Adult↗
PubMed1990

Camembert, Listeria and the immunocompromised patient.

Listeriosis is a rare but well known infectious complication in pregnant women and immunocompromised patients. Epidemiological studies have shown an association between listeriosis and alimentary contamination by listeria of a variety of foodstuff including soft, ripened cheeses. We describe two case-reports of listeria meningitis with high evidence of food-related illness due to the consumption of contaminated camembert. These observations urged our State Department of Health to formulate a communication about alimentary listeriosis at the intent of all health care professionals, including recommendations for patients at risk.

Aged↗