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Biomedical subjects

M Rabinovich

Publications and source records attributed to M Rabinovich.

At least 19 recordsLinked to original sources

Dynamical encoding by networks of competing neuron groups: winnerless competition.

Following studies of olfactory processing in insects and fish, we investigate neural networks whose dynamics in phase space is represented by orbits near the heteroclinic connections between saddle regions (fixed points or limit cycles). These networks encode input information as trajectories along the heteroclinic connections. If there are N neurons in the network, the capacity is approximately e(N-1)!, i.e., much larger than that of most traditional network structures. We show that a small winnerless competition network composed of FitzHugh-Nagumo spiking neurons efficiently transforms input information into a spatiotemporal output.

Action Potentials↗

Model of transient oscillatory synchronization in the locust antennal lobe.

Transient pairwise synchronization of locust antennal lobe (AL) projection neurons (PNs) occurs during odor responses. In a Hodgkin-Huxley-type model of the AL, interactions between excitatory PNs and inhibitory local neurons (LNs) created coherent network oscillations during odor stimulation. GABAergic interconnections between LNs led to competition among them such that different groups of LNs oscillated with periodic Ca(2+) spikes during different 50-250 ms temporal epochs, similar to those recorded in vivo. During these epochs, LN-evoked IPSPs caused phase-locked, population oscillations in sets of postsynaptic PNs. The model shows how alternations of the inhibitory drive can temporally encode sensory information in networks of neurons without precisely tuned intrinsic oscillatory properties.

Animals↗

Model of cellular and network mechanisms for odor-evoked temporal patterning in the locust antennal lobe.

Locust antennal lobe (AL) projection neurons (PNs) respond to olfactory stimuli with sequences of depolarizing and hyperpolarizing epochs, each lasting hundreds of milliseconds. A computer simulation of an AL network was used to test the hypothesis that slow inhibitory connections between local neurons (LNs) and PNs are responsible for temporal patterning. Activation of slow inhibitory receptors on PNs by the same GABAergic synapses that underlie fast oscillatory synchronization of PNs was sufficient to shape slow response modulations. This slow stimulus- and neuron-specific patterning of AL activity was resistant to blockade of fast inhibition. Fast and slow inhibitory mechanisms at synapses between LNs and PNs can thus form dynamical PN assemblies whose elements synchronize transiently and oscillate collectively, as observed not only in the locust AL, but also in the vertebrate olfactory bulb.

Animals↗

Successful removal of German yellowjackets (Hymenoptera: Vespidae) by toxic baiting.

Vespula germanica (F.) is a social vespid that has invaded many parts of the world, including Argentina. This wasp usually becomes a pest, affecting several economic activities. It also may impact the host community through predation or competition. The purpose of our study was to field test toxic baiting for reduction of wasp abundance. Wasps were poisoned with 0.1% fipronil mixed with raw minced beef in two beech forest sites on 20 February 2000 in northwestern Patagonia. All nests (46) within the two 6-ha sites with poisoned bait stations were killed, whereas Malaise traps in those sites captured 81.1% fewer wasps at the end of the season than traps in the two control sites. The average reduction of forager wasps on nontoxic baits was 87%. Fipronil was very effective in controlling wasp numbers, although there are limitations to the method, especially concerning conservation purposes. Toxic baiting can be useful in controlling wasp numbers in honey bee hive yards, farms, and parks.

Animals↗

Basic principles for generating motor output in the stomatogastric ganglion.

The lobster stomatogastric ganglion contains 30 neurons and when modulated can produce two distinct rhythmic motor patterns--the gastric mill and the pyloric. The complete neural circuitry underlying both patterns is well known. Without modulatory input no patterns are produced, and the neurons fire tonically or are silent. When neuromodulators are released into the ganglion from specific neurons or are delivered as hormones, the properties of the neurons and synapses change dramatically and modulator-specific gastric mill and pyloric patterns are produced. In general the rhythmicity derives from the induced burstiness of the neurons, and the pattern from the strengths of the electrical and chemical synapses. The organized activity can be traced to a marked reduction of chaotic activity in individual neurons when they shift from the unmodulated to the modulated state.

Animals↗

p53 and PCNA expression in advanced colorectal cancer: response to chemotherapy and long-term prognosis.

In a series of 71 patients with advanced colorectal cancer treated with biochemically modulated 5-fluorouracil (5-FU) and methotrexate (MTX), we investigated the relationship between the proliferating-cell nuclear antigen (PCNA) (PC10) and p53 (Pab1801) primary-tumor immunohistochemical expression with respect to clinical response and long-term prognosis. Nuclear p53 expression was demonstrated in 44% of samples (any number of positive tumor cells) while all tumors showed a certain degree of PCNA immunostaining. PCNA immunostaining was correlated with histopathologic grade and p53 expression, while p53 was not correlated with any of the parameters considered. The probability of clinical response to biochemically modulated 5-FU was independent of p53 and PCNA expression. p53 expression (all cut-off values) was not associated with short- or long-term clinical prognosis, whereas patients with higher PCNA primary-tumor expression showed longer survival from treatment and survival from diagnosis, according to univariate and multivariate analysis, particularly in the sub-set of colon-cancer patients. We conclude that the clinical response of advanced-colorectal-cancer patients to biochemically modulated 5-FU and MTX cannot be predicted by PCNA and p53 primary-tumor expression, but high PCNA expression appears to be independently related to long-term prognosis.

Adult↗

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Adult↗

Metastatic pattern and DNA ploidy in stage IV breast cancer at initial diagnosis. Relation to response and survival.

Sixty-nine patients with metastatic breast cancer (MBC) at initial diagnosis were analyzed to verify if metastatic pattern and clinical outcome are related to DNA ploidy determined by flow cytometry (FCM). Characteristics of 55 fully evaluable patients were as follows: median age: 61 years; postmenopausal: 75%; bone-only metastases (BM): 60%; extraosseous-only metastases (EM): 40%. Overall response rates (CR + PR) obtained with different chemotherapies and/or hormonal therapies were 58% and 68% for patients with BM and EM, respectively. Sixty percent of specimens resulted aneuploid, and the mean coefficient of variation of the complete series was 5.1%. In the whole group of patients DNA ploidy of primary tumor did not predict the metastatic pattern and had no influence upon response to treatment, duration of response, time to progression, and overall survival. When analyses were carried out according to metastatic pattern, those patients with BM showed similar results. However, within the group with EM, those with diploid tumors presented a significantly better survival (median 18 vs 13 months, p = .04). FCM-DNA analysis seems to identify a subgroup of patients with poor prognosis constituted by those who had aneuploid primary tumors and metastases to extraosseous sites.

Adenocarcinoma↗

Carboplatin plus ifosfamide as salvage treatment of epithelial ovarian cancer: a pilot study.

PURPOSE: This study aimed to evaluate the activity and toxicity of carboplatin (PPL) and ifosfamide (IFO) in patients with epithelial ovarian cancer previously treated with cisplatin (CDDP)-containing regimens. PATIENTS AND METHODS: From July 1989 to December 1991, 35 patients with epithelial ovarian cancer relapsed or refractory to CDDP as first-line chemotherapy were treated. PPL was administered at a dose of 300 mg/m2 intravenously (IV) on day 1 and IFO at a dose of 1,500 mg/m2 IV on days 1 to 3 every 3 to 4 weeks. Criteria for evaluating previous response to CDDP were strictly defined. RESULTS: The overall response rate was 43% (complete response [CR], 6%; partial response [PR], 37%) and the median duration of response was 7 months (range, 3 to 16). In potentially platinum-sensitive (PPS; relapsed) patients, the overall response rate was 56%. None of the primary platinum-resistant (PPR) patients obtained a clinical response to PPL plus IFO, whereas one of five secondary platinum-resistant (SPR) patients obtained a PR. The regimen was easily manageable. CONCLUSION: PPL plus IFO is useful and well-tolerated combination in salvage treatment of patients with advanced ovarian cancer. However, clear synergism between PPL and IFO that could overcome intrinsic or acquired CDDP resistance was not observed. The advantage of PPL plus IFO as compared with CDDP-containing regimens is represented by the increased tolerability and the reduced neurotoxicity, nephrotoxicity, and ototoxicity as compared with CDDP-containing regimens. It is essential that the patient population be defined according to their previous response to platinum therapy in trials involving second-line therapy of ovarian cancer.

Adult↗

Development and validation of prognostic models in metastatic breast cancer: a GOCS study.

The significance of several prognostic factors and the magnitude of their influence on response rate and survival were assessed by means of uni- and multivariate analyses in 362 patients with stage IV (UICC) breast carcinoma receiving combination chemotherapy as first systemic treatment over an 8-year period. Univariate analyses identified performance status and prior adjuvant radiotherapy as predictors of objective regression (OR), whereas the performance status, prior chemotherapy and radiotherapy (adjuvants), white blood cells count, SGOT and SGPT levels, and metastatic pattern were significantly correlated to survival. In multivariate analyses favorable characteristics associated to OR were prior adjuvant radiotherapy, no prior chemotherapy and postmenopausal status. Regarding survival, the performance status and visceral involvement were selected by the Cox model. The predictive accuracy of the logistic and the proportional hazards models was retrospectively tested in the training sample, and prospectively in a new population of 126 patients also receiving combined chemotherapy as first treatment for metastatic breast cancer. A certain overfitting to data in the training sample was observed with the regression model for response. However, the discriminative ability of the Cox model for survival was clearly confirmed.

Analysis of Variance↗

Morphological findings contributing to a failed Fontan procedure. Twelve-year experience.

A group of 37 patients (age range, 3 months to 29 years) who died after the modified Fontan procedure (within 2 months), representing 15% of the 245 patients undergoing this procedure from 1976 through 1988, was reviewed to determine the causes of death. The three morphological groups were 1) univentricular atrioventricular connection (n = 19), 2) tricuspid atresia (n = 9), and 3) other complex malformations (n = 9). Subaortic stenosis was present in 15 patients (40%) in this group compared with 31 of 208 early survivors (15%) (p = 0.008). Pulmonary artery banding, identified as a risk factor in our previous experience, was performed in 14 patients, nine of whom had subaortic stenosis. Nine palliative procedures for subaortic stenosis were performed in eight patients--before the Fontan procedure in three patients and concurrently with the Fontan procedure in five patients. Myocardial hypertrophy and signs of acute ischemic injury were common findings at autopsy (n = 25) and were particularly prominent in all patients with univentricular heart of left ventricular morphology associated with subaortic stenosis and previous pulmonary artery banding (n = 7). We conclude that the present majority of deaths occurring after the modified Fontan procedure are myocardial in nature and attributable to advanced myocardial hypertrophy that is potentiated by previous pulmonary artery banding and subaortic stenosis.

Aortic Valve Stenosis↗

[Pure testicular seminoma. Experience in treatment of 44 patients].

The records of 44 patients with pure testicular seminoma treated from 1981 to 1989 were reviewed. Twenty-one patients (48%) had stage I disease; 16 patients (36%) stage IIA; 4 patients (9%) stage IIB and 3 patients (7%) stage III. A previous history of cryptorchism was present in 7 patients (16%); testicular trauma in 9 patients (20%); orchiepididymits in 1 patient (2%) and genitourinary malformation in 1 patient (2%). Typical seminoma was observed in 43 patients (98%) and anaplastic seminoma in the remaining one (2%). There were no patients with spermatocytic seminoma. An elevated level of beta-human chorionic gonadotropin persisting after orchiectomy was found in 6 patients (14%). Syncytiotrophoblastic giant cells were identified after serial sections of the surgically resected tissue in two patients. Levels of this serum marker returned to normal values after primary treatment in all patients. Overall survival for all patients is 96% at 8 years. This corresponds to 100% for stages I, IIA and IIB and to 33% (1/3) for state III. Two patients (5%) presented recurrent disease in extralymphatic territories. Both of them were successfully rescued with proper therapy. Treatment was generally well tolerated and toxicity was mild to moderate.

Adolescent↗

Cardiotoxicity as a result of 5-fluorouracil therapy.

We report the case of a patient bearing a sigmoid colon carcinoma, stage IV, who after 11 months of antiblastic therapy, having completed a dose of 81,000 mg of 5-FU and CCNU, suffered a myocardial infarct. We attribute this complication to 5-FU. Due to the fact that the coronary angiogram did not confirm the arteriosclerotic nature of the lesion, we suggest that it could have been caused by an endoarteritis, resulting from an immuno-allergic or toxic cumulative process.

Adenocarcinoma↗