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Biomedical subjects

R Rago

Publications and source records attributed to R Rago.

At least 19 recordsLinked to original sources
PubMed2005

Randomized clinical trial comparing regional and general anaesthesia in minimally invasive video-assisted parathyroidectomy.

BACKGROUND: This randomized clinical trial was performed in a single institution to compare the results of minimally invasive video-assisted parathyroidectomy (MIVAP) conducted under regional anaesthesia (RA) or general anaesthesia (GA). METHODS: Fifty-one patients undergoing MIVAP for primary hyperparathyroidism were assigned randomly to either RA (26 patients) or GA (25). RA involved a bilateral deep cervical block, and local infiltration of the incision site with a mixture of 0.25 per cent lignocaine and 0.15 per cent bupivacaine. GA was induced by intravenous administration of propofol, remifentanil and rocuronium bromide. RESULTS: The two groups were matched for age, sex, adenoma size, and preoperative serum calcium and parathyroid hormone levels. The interval from skin incision to closure was similar in the two groups (27.6 and 25.8 min for RA and GA respectively), whereas the total operating time (from induction of anaesthesia to return to the ward) was significantly lower with RA (72.1 versus 90.2 min; P = 0.001). The postoperative requirement for pain medication, measured in terms of amount of ketorolac administered at the request of the patient, was significantly lower in the RA group (28.5 versus 80 mg/day; P < 0.001). CONCLUSION: MIVAP performed under RA was associated with a shorter overall operating time and a reduced need for postoperative pain relief.

Adult↗
PubMed2001

Mood and behavioural disorders following traumatic brain injury: clinical evaluation and pharmacological management.

In order to investigate phamacotherapeutic responsiveness of major depression and other behavioural disturbances associated with traumatic brain injury (TBI), 20 post-TBI patients were diagnosed as being depressed by two independent neuropsychiatrist observers, out of 37 consecutive TBI subjects sent to psychiatric counselling for poor compliance during rehabilitation programmes or psychiatric/behavioural disturbances after return to society. They were subsequently divided into two subgroups, depending on time elapsed from trauma (A: within 6 months; B: at 24-36 months post-trauma) and were enrolled in an open informed pharmachological study. Rating at baseline included Glasgow Coma Score on hospital admission, length of coma, length of hospitalization, Functional Independence Measure (FIM), Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression scale (CGI). BPRS and CGI were repeated after 12 weeks of oral administration of citalopram (20 mg a day) and carbamazepine (600 mg a day). At baseline, psychiatric symptoms in group B were worse than in group A (particularly somatic overconcern, anxiety, depressed mood, psychomotor slowness, inappropriate and labile affect). At T1, the global (group A and B combined) CGI and BPRS scores showed a statistically significant improvement when compared with T0, even if group B scores remained higher than group A. The results of this study suggest that: (a) citalopram combined with carbamazepine is effective in reducing depression and behavioural disorders following TBI, and (b) these disturbances should be addressed as soon as possible during the acute rehabilitation period.

Adult↗
PubMed2000

Fatty acid composition of spermatozoa and immature germ cells.

A great deal of attention has recently been given to the essential role of polyunsaturated fatty acids (PUFA) of sperm membranes. We studied the fatty acid composition of the immature germ cells (IGC) and of the sperm populations separated by Percoll gradient in the ejaculate of normozoospermic patients. Fatty acid pattern was analysed by combined gas chromatography-mass spectrometry on a capillary column. In IGC, differences were found compared with mature spermatozoa, with a higher percentage of saturated fatty acids and of essential fatty acids. On the contrary, the long-chain PUFA were significantly lower in IGC. The highest concentration of n3 PUFA docohexaenoic acid (DHA) was detected in the spermatozoa deriving from 70-100% Percoll layers and a direct linear correlation was found between the increase of DHA and increased percentage of Percoll gradient. An inverse relationship between the percentage of atypical sperm forms in each layer and the percentage of DHA was also observed. This study demonstrates that the human germ cell line can elongate and desaturate essential fatty acids and that the percentage of long-chain PUFA is correlated with the normal morphology of sperm cells.

Fatty Acids↗
PubMed1999

Efficacy of suramin against human prostate carcinoma DU145 xenografts in nude mice.

PURPOSE: Toward developing a model to study the mechanism of action of suramin against prostate cancer, we identified the effect of suramin on the growth of xenografts of the androgen-independent human prostate carcinoma DU145 cell line and our subline of suramin-resistant (SR) DU145 cells which are less responsive to suramin in vitro. METHODS: Athymic nude mice bearing DU145 or SR DU145 xenografts were treated intraperitoneally (IP) once weekly with normal saline (vehicle control) or suramin in normal saline. For data analysis mice were grouped as follows: 0 mg/kg (controls), < 210 mg/kg, 210 to 260 mg/kg, or >260 mg/kg suramin. RESULTS: The growth of DU 145 xenografts was slowed by treatment with 210 to 260 mg/kg suramin IP once weekly: differences in tumor volume for the 210 to 260 mg/kg group compared with the control group on days 29 and 57 showed growth inhibited by 43% and 55%, respectively. At the same time, growth of SR DU 145 xenografts generally was not slowed by suramin treatment at any dose, but appeared to be enhanced to some degree by all doses of suramin during the typical slower initial growth phase of xenografts of this cell line: differences in tumor volume compared with control on day 29 showed growth enhanced by 100% to 342%. Mice treated with 210 to 260 mg/kg maintained nadir suramin plasma levels near our clinically relevant target of 1 x 10(-4) M. CONCLUSIONS: Suramin, without concomitant corticosteroid therapy, was effective in slowing the growth of DU145 xenografts in nude mice at clinically relevant plasma suramin levels. The data showing efficacy for DU145 xenografts was supported by the lack of efficacy at the same time for xenografts of cells known to be less responsive to suramin in vitro, i.e. the SR DU145 cells, at similar doses and nadir plasma suramin levels. In discussions on the utility of suramin our data should be considered as support for continuing the study of suramin in the treatment of advanced, androgen-independent prostate cancer.

Animals↗
PubMed1998

Management of Hormone-Sensitive and Hormone-Refractory Metastatic Prostate Cancer.

BACKGROUND: Prostate cancer is a significant health problem in the United States and is the focus of increasing attention in our society. With the aging of the US population, it is likely that prostate cancer will continue to grow in importance. The options for systemic therapy of metastatic prostate cancer should be familiar to physicians, including nonspecialists, whose patients seek their advice and counsel. METHODS: Past and recent literature was surveyed to provide an understanding of the systemic treatment of advanced prostate cancer. The author presents a review of the systemic treatment of metastatic prostate cancer in different clinical circumstances and addresses the current status of chemotherapy in the management of advanced prostate cancer. RESULTS: Early androgen deprivation used over prolonged periods appears to be modestly superior to delayed androgen deprivation with a small potential survival advantage and an advantage in delaying disease progression in advanced prostate cancer. Patients with hormone-refractory prostate cancer may benefit from secondary hormonal therapy (eg, adrenal enzyme inhibitors, antiandrogens, glucocorticoids) and chemotherapy. CONCLUSIONS: The choices of therapy for metastatic prostate cancer depend on individual patient preference. Patients and physicians should be aware of the possible side effects associated with the therapeutics options for treatment of metastatic prostate cancer.

Journal Article↗
PubMed1998

Renal clearance, tissue distribution, and CA-125 responses in a phase I trial of suramin.

Suramin was administered to 49 patients in a Phase I cancer trial with real-time pharmacokinetic monitoring and dose individualization to achieve targeted mean plasma concentrations of 210 and 155 mg/liter during the 7-day period between days 15 and 22. Pharmacokinetic sampling after doses on days 1, 3, 5, and 8 was used to modify weekly suramin doses, beginning on day 15, in an attempt to achieve specific averaged plasma concentrations of 210 and 155 mg/liter. A 200-mg test dose was not effective in prospectively determining individual pharmacokinetic parameters and dosage requirements. Patients with peak plasma suramin concentrations in excess of 350 mg/liter may be more likely to experience neurotoxicity (P = 0.06), but there was no statistically significant effect of peak suramin concentration or of cumulative dose. Biopsy and autopsy tissue samples demonstrated low penetration of suramin into brain tissue and muscle but good penetration into prostate and other visceral organs. Prospective use of surrogate substrates for CYP1A2, CYP3A3/4, and CYP2D6 showed no consistent effect of suramin on these enzymes. Although a correlation between creatinine clearance and suramin renal clearance was found (r2 = 0.38; P < 0.00005), there was no correlation between creatinine clearance and total suramin clearance (P = 0.21). No suramin dose modification for renal or hepatic dysfunction can be supported at this time. Three of four ovarian cancer patients demonstrated a drop in CA-125 serum concentrations during suramin treatment.

Adult↗
PubMed1997

Antisperm antibody detection: 2. Clinical, biological, and statistical correlation between methods.

PROBLEM: In clinical andrology, the detection of antisperm antibodies (ASA) is regarded as one of the most important steps in the study of male infertility. This practice is generally accepted even though there is still some disagreement about the true meaning of antisperm immunity, and there remains a good deal of controversy about the test regarded as the most suitable for the detection of antibodies directed against sperm antigens. International Workshops have tried to standardize universally accepted protocols. A panel of three or four methods is generally advised to provide a correct and complete screening of patients with antisperm immunity. The aim of the present paper is to report our studies on the correlation between direct methods (IBT, MAR test) and indirect methods (gelatin agglutination test [GAT], and tray agglutination test [TAT]) and to establish whether biological models can explain the antibody test results. An attempt was also made to establish a "predictive threshold" to explain even apparently discordant direct and indirect results.

Agglutination Tests↗
PubMed1995

Use of a DNA microfluorometric assay to measure proliferative response of mink lung cells to purified TGF beta and to TGF beta activity found in prostate cell conditioned medium.

The proliferative response of Mv1Lu cells to purified TGF beta 1, or TGF beta-like activity released by various cells into medium conditioned over a 24-h period was quantitated by adapting a rapid DNA fluorometric assay. Acid activation of the conditioned medium allowed the amount of biologically latent versus active TGF beta to be quantitated. A neutralizing antibody specific for TGF beta 1, 1.2, and 2.0 completely blocked the growth inhibition observed treating Mv1Lu cells with either purified TGF beta 1 or medium containing secreted TGF beta-like activity conditioned by DU145 prostate cells. In contrast to other assays commonly used to measure TGF beta activity, the proliferative response is related directly to DNA content rather than as a reflection of enzymatic activity or incorporation of 3H-thymidine. The necessity for radioactive isotope usage has been eliminated, and the biological response can be quantitated over a period of days.

Animals↗
PubMed1993

Effects of suramin on the proliferation of primary epithelial cell cultures derived from normal, benign hyperplastic and cancerous human prostates.

Primary epithelial cultures (PECs) derived from normal, benign hyperplastic (BPH), and cancerous human prostate tissue were treated with increasing doses of suramin, and assayed for cell proliferation over a period of days. The suramin IC50 (inhibitory concentration 50%) value was 0.5 to 1.0 x 10(-4) M, whereas doses between 2.5 x 10(-4) and 5 x 10(-4) M resulted in total growth inhibition. This inhibition was reversible by exchange with suramin-free medium up to day 6. Concentrations > or = 5 x 10(-4) M resulted in increased cytotoxicity as exposure time increased. No differential response to suramin could be demonstrated among the prostate PECs derived from different tissues. The established cell lines, PC-3 and DU 145, grown in serum containing medium exhibited IC50s comparable to the PECs grown in serum free medium. EGF, bFGF, alpha, or beta ECGF at the concentrations tested did not reverse suramin inhibition. Increasing concentrations of bovine pituitary extract (BPE) increased cell growth in both the treated and the control cells. However, the percent growth inhibition by suramin at each concentration of BPE remained constant. Flow cytometry examination of cells treated for 7 days with suramin (0-10(-3) M) failed to detect any significant cell cycle alterations compared to control. At high concentrations of suramin (> or = 10(-4) M), large numbers of viable and dead cells were detectable in the medium. The increase in unattached viable cells was most prevalent (80%) in cultures treated with suramin at the time of plating, but also occurred with cells (25-30%) plated hours prior to the addition of suramin. Treatment for several days with low concentrations of suramin (10(-7) to 10(-5) M) transiently enhanced cell growth compared to controls.

Cell Adhesion↗
PubMed1993

Evidence of an absorption phase after short intravenous suramin infusions.

Suramin was given as an intravenous infusion to 16 cancer patients in a phase I trial. Individual pharmacokinetic parameters were calculated from a test dose given 1 week prior to the administration of a full-dose (350-700 mg/m2) regimen of 1-h loading and maintenance infusions. A distribution phase of 3.8 h was found. Plasma suramin concentrations were noted to increase following cessation of the intravenous test infusion in eight subjects. A model is proposed in which high-capacity, low-affinity binding of suramin to a shallow compartment adjacent to the intravascular space occurs rapidly during infusion, followed by absorption back into the measured blood pool with binding to plasma albumin. Despite the observable presence of this postinfusion peak shortly after the cessation of the brief suramin infusion, the pharmacokinetics of suramin were best characterized by a traditional two-compartment model. The dose-adjusted area under the concentration-time curve (AUC) increased with dose, supporting a hypothesis of sustained absorption of suramin to vascular endothelium but also raising the possibility of dose-dependent clearance.

Absorption↗
PubMed1991

Disruption of cellular energy balance by suramin in intact human prostatic carcinoma cells, a likely antiproliferative mechanism.

The antiparasitic drug, suramin, has antiproliferative effects in human carcinoma cells. It has been suggested that this occurs through blockade of growth factor-receptor interactions. Three types of evidence that suramin rapidly inhibits cellular respiration or disrupts cellular energy balance in intact cells of the human prostate carcinoma cell line, DU145, are presented. Beginning at approximately 10(-4) M, suramin rapidly causes dose-dependent inhibition of tetrazolium conversion by mitochondrial dehydrogenases in intact cells, demonstrating an inhibition of respiration. This effect is reversed by exchange with suramin-free media but not by pretreatment with serum, epidermal growth factor, insulin-like growth factor I, acidic and basic fibroblast growth factors, or calcium. Rhodamine 123 (10 micrograms/ml) uptake by mitochondria in intact DU145 cells is inhibited in the presence of 10(-3) M suramin. Treatment with 10(-4)-10(-3) M suramin causes the loss of rhodamine 123 from cells with mitochondria prestained with rhodamine 123, indicating that suramin is acting as an ionophore or respiratory poison. Also shown by electron microscopy are progressive toxic changes in mitochondria of DU145 cells within 1 h after treatment with 10(-4) M suramin. These data indicate that in intact DU145 cells 10(-4) M suramin rapidly disrupts cellular energy balance or respiration as seen by three studies of mitochondrial state. Disruption of energy balance or respiration represents a likely antiproliferative mechanism, as is thought to be a primary mechanism for the action of suramin in parasitic diseases. This proposed mechanism of action for suramin can explain the most prominent observed clinical toxicities of nephrotoxicity, adrenal toxicity, coagulopathy, and demyelinating neuropathy.

Biological Transport↗
PubMed1990

DNA fluorometric assay in 96-well tissue culture plates using Hoechst 33258 after cell lysis by freezing in distilled water.

A simple assay is described using bisbenzimidazole (Hoechst 33258) to determine cellular DNA content in 96-well tissue cultures plates. At time points of interest, the plates are emptied of media and stored frozen. When the assay is to be performed, cultures are briefly incubated in distilled water and frozen again. This process lyses the cells and allows rapid and thorough mixing of the fluorochrome and cellular DNA. Freezing permits convenient storage of cultures until the time of assay. Experiments can be batched, further reducing processing time and giving better intra- and interexperimental standardization. The assay generates a linear standard curve for DNA fluorescence versus cell number, the range of which is appropriate for microculture wells. This enables the rapid and accurate measurement of cell number involving minimal processing time, making this assay well suited for cell proliferation studies.

Bisbenzimidazole↗
PubMed1975

[The behavior of the hospitalized child awaiting a surgical operation].

The literature and personal experience are referred to in an assessment of psycho-affective situations in hospitalised children awaiting non-emergency surgery (appendicectomy, adenotonsillectomy, inguinal hernia, phymosis, hypospadias, cryptorchidism). Psychological and somatic damage resulting from an absence of preparation before hospitalisation and during admission immediately prior to surgery is described. A method whereby this may be avoided as far as possible with the aid of relatives is described.

Affective Symptoms↗
PubMedDate not supplied

Adjuvant trazodone in the treatment of alcoholism: an open study.

Serotonergic drugs have been proven to be helpful to alcoholics in maintaining abstinence. In this open study, we report that the atypical antidepressant trazodone at low doses was able to significantly decrease craving for alcohol, depressive, and anxious symptoms in a number (25) of detoxified alcohol-dependent subjects after 3 months of treatment. Trazodone may, therefore, be an adjuvant in the therapy of alcoholism.

Alcoholism↗