How do normal subjects learn a simple adaptative task: How and why do paranoid schizophrenic patients fail?

Summary The authors studied the behavior of normal subjects and paranoid schizophrenic patients in a simple problem-solving situation. The schizophrenics were divided into two sample groups, one of individuals under treatment and the other of individuals not under treatment.The learning process involved in this problem-solving situation is very similar to an instrumental conditioning, and can be understood by means of the following assumptions: (1) the subjects use decision functions in reacting to the stimuli, although they may be not fully aware of this; (2) learning is the result of successive transformations of these decisions in the course of time; (3) the changes have specific probabilities and are related to (a) those responses which are made to the latest stimuli, and (b) a differential probability for decision functions which were effective, or only interrupted painful reinforcement, or were completely ineffective.In schizophrenics further factors of importance were (1) an inertia factor and (2) the rigidly continued use of unsuccessful or only partially successful decision criteria.The authors used a systems theory based on Galois field theory and a calculus of operators specifying three groups of subjects. A computer program based on these hypotheses was tested in a simulation experiment.The statistical evaluation of the results showed a congruence between the theoretical approach and the experimental data.This work was carried out with financial support from the Institute de Alta Cultura, Lisbon, between 1970 and 1974     

Quantitation of adriamycin in plasma and urine: comparative study of radioimmunoassay and high-performance liquid chromatography methods

The response of tumours to adriamycin, and the cardiotoxicity of the drug, may be related to its pharmacokinetics and plasma levels. Rapid and sensitive methods of adriamycin determination in plasma and urine samples are thus needed. A comparative study shows that high-performance liquid chromatography with fluorimetric detection is a reliable and specific method, but it is relatively slow and sometimes lacks sensitivity. A commercially-available radioimmunoassay kit is convenient, but there is a cross reaction with the major metabolise adriamycinol and unless the assay is combined with an extraction step, it gives erroneously high results.     

Detrimental effect of neoadjuvant chemotherapy in patients with stage-iiib carcinoma of the cervix - results of a randomized trial

With the objective of testing the value of neoadjuvant chemotherapy in patients with stage III B carcinoma of the cervix, we began in 1984 a randomized, phase III trial comparing BOMP chemotherapy followed by pelvic radiotherapy versus pelvic radiotherapy alone. Patients were stratified by age, extension of parametrial involvement, and lymphangiographic findings. Despite a higher complete response rate, the overall 5-year survival was significantly inferior in the combined therapy group (39% vs 23%, P=0.02). Toxicity was more pronounced in the chemoradiation arm and 4 patients developed fatal pulmonary complications. Patterns of failure were similar in both groups. The use of primary chemotherapy in advanced carcinoma of the cervix was detrimental to the patients and its use outside a protocol setting is discouraged.     

Pseudomixoma peritoneal tipo adenomucinosis peritoneal diseminada con imágenes radiológicas atípicas

Pseudomyxoma peritonei is an unusual condition that has caused much confusion regarding its aetiology, clinical manifestations, treatment and prognosis. It is characterised by mucinous ascites and diffuse mucinous invasions of the peritoneum. Three histological subtypes have been defined: a) disseminated peritoneal adenomucinosis (peritoneal lesions composed of abundant extra-cellular mucin containing scant simple-to-focally-proliferating mucinous epithelium with little cytological atypia or mitotic activity); b) peritoneal mucinous carcinomatosis (peritoneal lesions composed of more abundant mucinous epithelium with the architectural and cytological features of carcinoma); and c) an intermediate group. The different histological subtypes have different prognoses. We report a case of disseminated peritoneal adenomatosis, and discuss its clinical management.     

Treatment variables in relation to oocyte maturation: Lessons from a clinical micromanipulation-assisted in vitro fertilization program

Objective: In an effort to understand the mechanism underlying the improved pregnancy rate observed in IVF cycles when gonadotropin-releasing hormone analogues (GnRH-a) are applied, we investigated a possible relationship between treatment variables and oocyte-nuclear maturity. Design: Nuclear maturity was retrospectively assessed in cumulus-free, denuded oocytes, obtained from women undergoing micromanipulation-assisted IVF treatment following controlled ovarian hyperstimulation with GnRH-a and menotropins. Setting: The setting was the infertility and IVF unit of a tertiary academic medical center. Participants: Two hundred twenty-one patients underwent 435 treatment cycles. Main Outcome Measure: This was the proportion of germinal vesicle-intact immature (GVII) oocytes. Results: One hundred fifty-four of the 3520 oocytes studied (4.4%) were in the GVII stage. These oocytes were found in 66 of the treatment cycles (15.2%) and in 54 of the patients (24.4%). Cycles in which GVII oocytes were detected did not differ from those in which all the aspirated oocytes were mature in the following respects: patient age, type and duration of infertility, controlled ovarian hyperstimulation protocol and time of ovum pickup. However, the GVII group was characterized by a significantly higher peak estradiol level, as well as a higher number of mature follicles visualized sonographically (diameter, >14 mm) and oocytes retrieved. Conclusions: Comparing the present findings with previously published data, it appears that the inclusion of GnRH-a in the stimulation regimen is associated with a lower proportion of immature oocytes. A higher occurrence of oocyte-nuclear immaturity is apparently associated with a significantly better ovarian response to stimulation. The high incidence of immature oocytes observed in patients with normospermic partners and low fertilization rates in previous cycles may suggest that the fertilization failure in some of these cases is due to oocyte, rather than sperm, dysfunction.     

Isolation and characterization of propagable cell lines (HUNC) from the androgen-sensitive Dunning R3327H rat prostatic adenocarcinoma

The Dunning H rat prostate tumor (R3327H) is a widely used experimental model of human prostatic adenocarcinoma (CaP). The Dunning H tumor has been characterized as androgen-sensitive, androgen-receptor (AR) positive, prostate-specific antigen and prostatic acid phosphatase (PAP) positive. To date, the tumor has been maintained by serial passage in vivo because of the lack of an in vitro cell line that retains the characteristics of the in vivo tumor. The objective of the present study was to establish a propagable cell line from R3327H adenocarcinoma that maintained androgen sensitivity and expression of AR, PSA and PAP. Tissue harvested from an in vivo R3327H tumor was dissociated with collagenase and placed into Richter's improved media (with supplements). A cytokeratin-positive epithelial cell line (HUNC- E) and a vimentin-positive stromal cell line (HUNC-S) were generated from the primary culture, subcultured continuously for >300 days, and passaged >50 times. Survival of the HUNC-E cell line in vitro depended on several media supplements, including nicotinamide, insulin, transferrin, selenium and epidermal growth factor (EGF). HUNC-E cells expressed AR and produced PSA and PAP throughout the culture period, as confirmed by immunocytochemistry and Western blot analyses. Addition of 14 nM testosterone (T) or dihydrotestosterone (DHT) to HUNC-E cells, stimulated DNA synthesis as well as anchorage-independent growth and PSA production, which demonstrated the androgen-sensitive nature of the cells in vitro. When HUNC-E and HUNC-S cells were combined in a 3:1 ratio and introduced subcutaneously into syngeneic male hosts, tumors formed in 2/3 animals with an average latency of 7 months. RT-PCR and immunocytochemical characterization of the HUNC cell lines revealed that the cells expressed several growth factors and their cognate receptors, including HGF, TGF-alpha and the TGF-betas, indicating the establishment of potential autocrine loops in the neoplastic cells. The HUNC-E and HUNC-S CaP cell lines, which retain the characteristics of the epithelial and stromal components of the in vivo R3327H tumor, will allow a more thorough and informative molecular and biological analysis of prostatic adenocarcinoma.      

Prophylactic percutaneous sealing of lumbar postdural puncture hole with fibrin glue to prevent cerebrospinal fluid leakage in swine

We explored the effect of fibrin glue injection at the site of dural puncture on cerebrospinal fluid (CSF) leakage in a swine model. Pigs were subjected to a lumbar dural CSF puncture in the sitting position with a 17-gauge Tuohy needle. Fibrin glue 1.4 mL was injected through the same needle into the epidural space. Evans blue dye was infused through the cisterna magna 15 min later, and the appearance of dyed CSF through the skin puncture and along the needle trajectory to the dura was inspected and categorized. In seven of eight animals, the CSF leak was sealed with fibrin glue. Control animals were injected with 1.4 mL saline. A sham operation group of animals underwent cisternal dye infusion without a lumbar puncture. CSF pressure at the cisterna magna was recorded throughout the procedure. No significant differences in the leakage indicators were found between the fibrin glue-injected and sham-operated group, whereas both groups showed significant differences with respect to the control group. The fibrin glue seal was effective against CSF pressures of 24.5 [17-31] cm H(2)O. We conclude that percutaneously injected fibrin glue is effective in stopping CSF leaks after dural puncture in this animal model. IMPLICATIONS: In this swine study, we repaired a cerebrospinal fluid leak after a dural puncture by percutaneously injecting tissue adhesive. The technique of percutaneous injection of fibrin glue seems promising for the prophylaxis of headache associated with cerebrospinal fluid leakage, and may be an alternative to an epidural blood patch.     

Acute hypoxic hypoxia transiently reduces GABA(A) binding site number in developing chick optic lobe

The Central Nervous System is known to be critically affected in the prenatal-perinatal period by hypoxic-ischemic insults, which produce several disorders such as loss of neural projections, increased susceptibility to seizures, apoptosis and an imbalance in normal activity of glutamatergic and GABAergic neurones, resulting in acute cell excitotoxicity. The aim of the present work was to establish a chick embryo model of normobaric acute hypoxic hypoxia as well as to evaluate modifications in GABA(A) receptor complex from chick optic lobe, that may result from this injury. Fertile chicken (Gallus gallus domesticus) eggs from White Leghorn were incubated and at embryonic days (ED) 12 to 18, subjected to a stream of 8%O(2)/92%N(2) during1 h, and then were either returned to their shelves in the incubator for recovery, or immediately processed for biochemical studies. Hypoxic treatment produced a significant age dependent reduction in GABA binding sites showing the greatest decrease at the earliest stages studied (ED12-ED16). Saturation curves of GABA binding performed at ED12 showed a decrease in B(max), (control, 5.48+/-0.20, hypoxic, 3.90+/-0.39 pmol/mg protein), but no significant change in K(d). Following 48 h in normoxic atmosphere post-hypoxia reduction in [3H]GABA binding was reversed. Pharmacological properties of GABA(A) receptor at ED12 showed that positive allosteric modulation effects of the steroid 3alpha-hydroxy-5alpha-pregnan-20-one and the barbiturate pentobarbital sodium were enhanced by the treatment. This model of acute prenatal hypoxic hypoxia produced marked alterations in inhibitory CNS neurotransmission that proved reversible and age dependent.