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Biomedical subjects

P Russo

Publications and source records attributed to P Russo.

At least 217 records · Page 12Linked to original sources

The role of pelvic lymphadenectomy and radical cystectomy for lymph node positive bladder cancer. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: The impact of pelvic lymph node dissection (PLND) on the survival of patients with lymph node positive bladder cancer is controversial. METHODS: The authors retrospectively analyzed the long term and disease free survival among 140 patients with lymph node positive disease having radical cystectomy and bilateral PLND at the Memorial Sloan-Kettering Cancer Center between 1980 and 1988. They also sought to identify prognostic variables for recurrence and survival. RESULTS: Of the 140 patients, 36 (25.7%) were found to be tumor free, with 22 (15.7%) followed longer than 5 years. Regression analysis identified P-category as the only prognostic parameter influencing survival. Patients with tumors confined to the bladder (< or = P3a) had a 52.6% 5-year survival rate compared with 23.4% among those with extravesical (> or = P3b) tumors. N-category was a significant predictor for recurrence but not survival. CONCLUSIONS: As judged from this analysis, radical cystectomy and a systematic PLND alone can provide favorable outcome in some patients with regional nodal metastases from bladder cancer. The survival advantage is most pronounced in patients with low stage primary tumors. Stage migration and patient selection may have biased these findings.

Combined Modality Therapy↗

High frequency jet ventilation: intraoperative application in infants.

The potential advantages of the intraoperative use of high frequency jet ventilation (HFJV) when compared with conventional ventilation (CV) include the maintenance of adequate gas exchange and lung function with a relatively motionless surgical field. To determine the pulmonary response to HFJV ventilation in infants during cardiac surgery, we evaluated lung function in nine infants supported with CV and HFJV during a Blalock-Taussig shunt procedure. Infants were randomized to each mode of ventilation with inspiratory and expiratory pressures and FiO2 held constant. Heart rate, blood pressure, arterial blood gases, pulmonary mechanics (lung compliance and resistance), and functional residual capacity (FRC) were compared after 10 minutes of stabilization of each ventilation mode, with the infants in the thoracotomy position and the surgical field adequately exposed. Pulmonary mechanics were measured using esophageal manometry and pneumotachography, and FRC by helium dilution. There was no difference in vital signs, pulmonary mechanics, FRC, or PaO2 on HFJV ventilation when compared with CV. Arterial PaCO2 was lower with a lower mean airway pressure on HFJV when compared with CV. The surgical team subjectively observed a diminished need for lung manipulation and improved ease of access to the surgical field with HFJV. These results indicate that the use of HFJV during closed-heart cardiac surgical procedures in infants provides similar cardiopulmonary stability and some potentially important clinical benefits when compared with CV.

Airway Resistance↗

TRPM-2 gene expression in normal rat ventral prostate following castration and exposure to diethylstilbestrol, flutamide, MK-906 (finasteride), and coumarin.

TRPM-2, not normally expressed in the rat ventral prostate, has been identified as an important genetic marker of castration-induced apoptotic cell death. It is not known whether other agents capable of causing growth inhibition of the rat ventral prostate also induce TRPM-2 expression. To investigate this further, 270 mature Sprague-Dawley rats were randomized into one of six groups: control, castration, diethylstilbestrol (DES), flutamide, MK-906 (finasteride), or coumarin. Five rats per group were sacrificed on days 1, 3, 5, 7, 10, and 21. Serum testosterone, body weights, and prostate weights were determined at each time point. The ventral prostate was removed and cellular RNA extracted. Northern blot analysis using cDNA probes for TRPM-2 and gamma-actin were performed at each time point. Only DES significantly decreased rat weights. DES and castration reduced serum testosterone to undetectable levels by the next day. Flutamide caused a 3.0- to 4.5-fold increase in serum testosterone above control. Coumarin and MK-906 did not affect serum testosterone levels. DES and castration reduced prostate weights to 20% and 6% of control, respectively, while inducing TRPM-2 expression to a maximum on day 5 of the experiment. DES induced TRPM-2 expression over a longer duration than did castration, suggesting that more than just the decrease of serum testosterone to castrate levels plays a role in the expression of TRPM-2. MK-906, coumarin, and flutamide reduced prostatic weights to a lesser extent (50%, 63%, 71% of control, respectively), but these agents did not induce TRPM-2 expression at any time during the experiment. TRPM-2 expression in the rat ventral prostate does not correlate simply with catabolic effects on the prostate.

Animals↗

Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer tissue.

The objective of this study was to test if specific insulin and insulin-like growth factor I (IGF I) receptors are expressed in ovarian cancer tissue. Thirteen tissue specimens from primary ovarian cancers, 1 specimen from a primary peritoneal carcinoma, 10 specimens from metastatic lesions of ovarian carcinomas, and 4 specimens from recurrent ovarian cancers together with 13 normal ovaries were tested for their content of insulin and IGF-I receptors, by the application of specific insulin and IGF-I receptor radioimmunoassays. The insulin receptor (IR) and IGF-I receptor (IGF R) content in the primary tumors varied between 23.8-321.4 and 16.4-554.2 ng/0.1 mg DNA, respectively. Metastatic lesions contained between 12.3 and 226.7 ng IR/0.1 mg DNA and between 7.5 and 459.4 ng IGF R/0.1 mg DNA. In recurrent tumors the receptor concentrations were in the range of 41.5-79.8 and 48.9-160.9 ng/0.1 mg DNA for insulin and IGF-I receptors, respectively. Normal ovarian tissue contained between 12.2 and 150.1 ng IR and between 21.4 and 420.1 ng IGF R per 0.1 mg DNA, respectively. As both insulin and IGF-I receptors are present in ovarian cancer tissue, the effects of insulin and IGF-I as potential growth factors in ovarian cancer should be further investigated.

Adult↗

Hypothermia enhances contractility in cerebral arteries of newborn lambs.

Hypothermia is the major factor influencing autoregulatory properties of the cerebral circulation in human infants undergoing hypothermic cardiopulmonary bypass. The present investigation evaluated the effect of decreased temperature on the contractility of isolated middle cerebral arteries obtained from newborn lambs. Reducing bath temperature from 37 to 21 degrees C caused a temperature-dependent increase in contractile tension, achieving 1.32 +/- 0.09 g above resting tension (0.75 g). Pretreatment with nonselective (alpha 1 and alpha 2) alpha-adrenoceptor antagonist, phentolamine (10(-5) M), with an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), and with a cyclooxygenase inhibitor, indomethacin (10(-5) M), did not affect the contractile response to a decrease in bath temperature from 37 to 21 degrees C. Furthermore, cerebral arteries were responsive to both norepinephrine (constriction) and sodium nitroprusside (relaxation) and the sensitivity of cerebral arteries to the sympathetic neurotransmitter norepinephrine appears to be enhanced at low temperatures. We postulate that direct cerebral vasoconstriction and enhanced adrenergic contractility may be responsible for increased cerebrovascular resistance during and after hypothermic cardiopulmonary bypass with possible ischemic cerebral injury and neurological sequelae.

Animals↗

Positive urinary cytology following a complete response to intravesical bacillus Calmette-Guerin therapy: pattern of recurrence.

The pattern of disease recurrence was examined in 75 patients with clinically undetectable positive urinary cytology results following a complete response to intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. A complete response was defined as negative cystoscopy and biopsy findings, urine cytology and flow cytometry (when available) for at least 1 year following therapy. Urinary cytology was positive in the absence of clinical disease at a median of 25 months (range 12 to 96) after BCG administration. Clinically recognizable disease (defined by a positive biopsy or visible papillary tumor) developed at a median of 6 months (range 2 to 60) after positive cytology was detected in 62 patients (83%), while 13 (17%) had persistently positive cytology results without an obvious source at a median of 6 months (range 2 to 29). The bladder was the single most common site of recurrence, with 39 recurrences developing in 36 patients (58%, 3 of whom had recurrent cancer after a complete response to each of 2 separate courses of BCG): 30 (77%) were superficial (stages Ta in 2, Tis in 25, Tis/T1 in 2 and T1 in 1) and 9 (23%) were invasive (stage T2+). Median interval to the detection of bladder recurrence following a positive cytology result was 6 months (range 2 to 50). Upper urinary tract disease developed at a median of 7 months (range 2 to 41) in 11 patients (18%), while 7 (11%) had a prostatic recurrence at a median of 5 months (range 2 to 60). There were 9 synchronous bladder and prostate (5) or upper tract (4) recurrences in 8 patients (13%) at a median of 22 months (range 2 to 40) in the former group and 15.5 months (range 3 to 20) in the latter group. Overall, of 75 sites of recurrence in 62 patients 48 (64%) were in the bladder, 15 (20%) in the upper urinary tract and 12 (16%) in the prostate. High risk patients with superficial bladder cancer who have clinically unconfirmed positive urinary cytology results following a complete response to intravesical BCG therapy require aggressive evaluation of intravesical and extravesical sites to detect the presence of persistent or progressive in situ or invasive disease.

BCG Vaccine↗

Myocutaneous flaps in genitourinary oncology.

Between January 1983 and September 1992, 32 myocutaneous flaps were fashioned in 28 patients for reconstruction following treatment of genitourinary malignancies or complex pelvic fistulas. Of the myocutaneous flaps 14 were used to obtain primary soft tissue coverage of large but otherwise uncomplicated wounds and 10 were used to cover previously irradiated resection sites. Four myocutaneous flaps were used to repair complex radiation-induced fistulas involving the bladder, vagina, urethra and rectum. Flaps were used to cover infected or nonhealing open wounds in 8 cases, 4 of which also had been previously irradiated. Myocutaneous flap donor sites were the tensor fascia lata in 11 cases, gracilis in 9, rectus abdominis in 10 and rectus femoris in 2. There was 1 major complication (flap loss) and 9 minor complications. There were no perioperative deaths. Myocutaneous flaps are an effective means of covering large groin, perineal and lower abdominal surgical defects after radical surgery.

Adolescent↗

Induction of DNA double-strand breaks by 8-methoxycaffeine: cell cycle dependence and comparison with topoisomerase II inhibitors.

We have studied the ability of 8-methoxycaffeine (8-MOC)--one of the most effective caffeine derivatives in inducing chromosomal aberrations--to induce DNA double strand breaks (DSB) in purified human T lymphocytes during the cell cycle. Etoposide- or ellipticine-mediated DNA break frequency was used as a parameter of topoisomerase II activity. DNA-DSB induced by either 8-MOC or VP16 or ellipticine rose co-ordinately with the level of DNA topoisomerase II and with the onset of DNA replication. At concentrations between 10 and 50 microM 8-MOC was approximately 75% as active in terms of DSB as VP16 and ellipticine. By contrast with VP16 and ellipticine, 8-MOC was not cytotoxic. In conclusion, our data suggest that 8-MOC is an agent that efficiently induces DNA-DSB at non-toxic concentrations, and without direct inhibition of topoisomerase II.

Caffeine↗

Circumvention of atypical multidrug resistance with tumor necrosis factor.

Some "multidrug-resistant" (MDR) cell lines are not associated with a defect in drug accumulation or with the overexpression of P-glycoprotein. These cell lines are defined as "atypical MDR" (at-MDR) and they often express altered or mutated topoisomerase II. We investigated the ability of tumor necrosis factor to reverse at-MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its efficacy in potentiating in vitro topoisomerase II-targeted drugs, and because there is convincing evidence that the synergy is due to an increased number of topoisomerase-associated strand-breaks as well as to an increased level of extractable topoisomerase.

DNA Damage↗

Experience with neoadjuvant diethylstilboestrol and radical prostatectomy in patients with locally advanced prostate cancer.

OBJECTIVE: To report our experience with neoadjuvant endocrine therapy and radical retropubic prostatectomy (RRP) in patients with locally advanced prostate cancer. PATIENTS AND METHODS: Fifty-five patients with prostatic adenocarcinoma (18 clinical stage B2/3, 27 clinical stage C, and 10 clinical stage D0) were treated with diethylstilboestrol (DES) 3 mg/d (median time 12 weeks, range 5-36) followed by pelvic lymph node dissection and planned RRP. Clinical response was monitored bi-weekly with serum prostate-specific antigen (PSA), serum acid phosphatase and digital rectal examination. RESULTS: The median pre-treatment serum PSA was 20.4 ng/ml (range 1.2-620). The median post-treatment, pre-operative serum PSA was 0.4 ng/ml. Twenty-seven (49%), 41 (75%) and 54 (98%) patients had serum PSA levels that were undetectable, < 1.0 ng/ml and < 4.0 ng/ml respectively. In 15 patients, transrectal ultrasound measurement of prostatic volume changes was performed, and all demonstrated prostate volume reduction (median reduction 35%, range 18-45). All 55 patients underwent pelvic lymphadenectomy, with 47 (85%) undergoing RRP. Of the eight patients not undergoing RRP, three had negative lymph nodes but prostate resection was not deemed feasible and five had nodal metastases as determined by frozen section analysis. Final pathological stage revealed the following distribution: organ confined tumours, 18 (33%); capsular perforation with negative surgical margins, seminal vesicles and lymph nodes, seven (13%); seminal vesicle and/or margin involvement with negative lymph nodes, 18 (33%); lymph node metastases, 12 (22%). Neither pre-therapy serum PSA nor serum PSA response was predictive of final pathological stage. With a median follow-up interval of 26 months (range 12-49), 21 patients (38%) have undetectable serum PSA without adjuvant therapy. CONCLUSIONS: Our results indicate that despite clinical evidence suggestive of downstaging, the majority of patients with locally advanced prostatic carcinoma managed with neoadjuvant DES and RRP continue to have pathological evidence of extraprostatic carcinoma.

Adenocarcinoma↗

A tiny renal renin-secreting tumor.

A small 5 mm renal renin-secreting tumor is described in a child. Suggestions are made to circumvent the difficulties in investigating such cases. It is stressed that the diagnosis is probably often missed especially in the case of very small tumors.

Adenocarcinoma↗

Oral soft tissue myxoma: report of a case and review of the literature.

The soft tissue myxoma of the oral cavity is a rare neoplasm. We report a case arising from the palate in a 15-year-old male. A review of the literature is presented with clinicopathologic, immunohistochemical, and ultrastructural data confirming the diagnosis. The pathogenesis and differential diagnosis are discussed with reference to documented association with fibrous dysplasia and "Carney syndrome."

Adolescent↗

Potentiation of TNF-mediated cell killing by mitoxantrone. Relationship to DNA single-strand break formation.

Tumor necrosis factor (TNF) is a pleiotropic cytokine that mediates different cellular responses including cytotoxicity, cytostasis, proliferation, differentiation and expression of specific genes. Recent studies have demonstrated that chemotherapeutic drugs that inhibit the nuclear enzyme DNA topoisomerase II synergize with TNF in tumor cell killing in vitro and in vivo. We now report that a combination of TNF and the topoisomerase II inhibitor Mitoxantrone produced dose-dependent synergistic cytotoxicity against the human ovarian cancer cell line A2774 in a clonogenic assay (1 hr treatment). This result was obtained with simultaneous administration of the drug and the cytokine under test, and is independent of modification of Mitoxantrone uptake. This combination is responsible for an evident augmentation of "cleavable complex" formation. From isolated nuclei, we have isolated also the topoisomerase II activity; we observed an increment when the cells were previously treated with TNF, 2.5 min before nuclear extraction. After 10-30 min of treatment with TNF, the topoisomerase II activity returned to normal values. If TNF is not given with but 30 min before Mitoxantrone, no potentiation of cytotoxicity or break induction is observed. These results suggest that specific timing of the association may be needed also when attempting to translate it to animals and humans.

Cell Death↗

Adult prostatic sarcoma.

A 57-year-old male with a high grade leiomyosarcoma of the prostate is presented. The local extent of the tumor was accurately described by magnetic resonance imaging (MRI). Following chemotherapy, the tumor volume was reduced by 60% and was judged to be clinically resectable by MRI. Despite radical cystoprostatectomy, the patient died of metastatic disease.

Humans↗

Dual regulation by heat and nutrient stress of the yeast HSP150 gene encoding a secretory glycoprotein.

We have cloned and characterized the HSP150 gene of Saccharomyces cerevisiae, which encodes a glycoprotein (hsp150) that is secreted into the growth medium. Unexpectedly, the HSP150 gene was found to be regulated by heat shock and nitrogen starvation. Shifting the cells from 24 degrees C to 37 degrees C resulted in an abrupt increase in the steady-state level of the HSP150 mRNA, and de novo synthesized hsp150 protein. Returning the cells to 24 degrees C caused a rapid decrease in mRNA and protein synthesis to basal levels. The HSP150 5'-flanking region contains several heat shock element-like sequences (HSE). To study the function of these sequences, a strain bearing a disrupted copy of the HSP150 gene was transformed with plasmids in which the coding region of HSP150, or a HSP150-lacZ fusion gene, was preceded by 5' deletion derivatives of the HSP150 promoter. Site-directed mutagenesis of one HSE-like element, located between the TATA box and transcription initiation sites, abolished heat activation of transcription. In addition to heat shock, the HSP150 gene is regulated by the availability of nutrients in the growth medium. The HSP150 mRNA level was increased by nitrogen limitation at 24 degrees C, even when under the control of a HSP150 promoter region of 137 bp carrying the mutagenized HSE.

Base Sequence↗

Interleukin-2 activity of colonic lamina propria mononuclear cells in a rat model of experimental colitis.

BACKGROUND: Altered interleukin 2 (IL-2) production has been implicated in the pathogenesis of inflammatory bowel diseases. METHODS: The temporal relationship between IL-2, prostaglandin E2 (PGE2) production, and mucosal injury was evaluated by isolated colonic lamina propria mononuclear cells (LPMC), using the trinitrobenzene sulfonic acid model of rat colitis. RESULTS: Spontaneous LPMC IL-2 activity was significantly increased in chronic (5 weeks) but not acute (5 days) or resolved colitis groups. IL-2 activity after concanavalin A activation was highest in the groups with resolved and chronic colitis. PGE2 production was significantly increased in LPMC cultures in acute or chronic colitis as well as the ethanol control groups but not the resolved colitis group. The addition of indomethacin to LPMC cultures decreased PGE2 levels in all groups, whereas IL-2 activity increased only for the chronic and resolved colitis groups. No correlation was found between PGE2 and IL-2 production by LPMC. CONCLUSIONS: In this experimental model, LPMC IL-2 production varied according to the severity and duration of the inflammation. Increased PGE2 production does not appear to be responsible for the IL-2 alterations in colitis.

Acute Disease↗

[Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

Animals↗

[Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. II. Study of the antibody response].

In an experiment of vaccination against caprine arthritis encephalitis virus (CAEV), the antibody response in three groups of young goats was followed by AGIDT, ELISA, seroneutralization, western blot. Goats of group I, inoculated with inactivated virus mixed with adjuvant, showed a few weeks after vaccination a high antibody response, clearly enhanced after infectious intraarticular challenge. These antibodies did not protect against arthritis, which appeared more severe in this group. In the other groups (group II, control adjuvant, with the weakest clinical expression, group III, control tissue culture medium), the levels of circulating antibodies appeared much lower. No neutralizing antibodies could be detected during the whole experiment. A western blot analysis revealed mainly in group I a high antibody response against gp 135 antigen. The important immune reaction might be involved in enhancement of viral infectivity in this group.

Animals↗