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Biomedical subjects

J Gallego

Publications and source records attributed to J Gallego.

At least 19 recordsLinked to original sources

Prevention of the acute neurotoxic effects of phenytoin on rat peripheral nerve by H7, an inhibitor of protein kinase C.

The neurotoxic effects of a single dose of phenytoin (150 mg/kg body weight) alone or 30 min after H7 (a protein kinase C inhibitor) injection (20 mg/kg body weight) were investigated in terms of peripheral neuromuscular function and Na+,K(+)-ATPase activity of the sciatic nerve. This intraperitoneal injection of phenytoin induced complete blockade of muscle action potentials in the dorsal segmental muscles of the rat tail evoked by electric stimulation of the caudal nerve and a 40% decrease in the Na+,K(+)-ATPase activity of the rat sciatic nerve when compared with control values, measured as the difference between total and ouabain-insensitive ATPase activity. Prior administration of H7 resulted in the complete prevention of both effects. Implications of protein kinase C inhibition in phenytoin neurotoxicity are discussed.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Implications of a consensus recognition site for phosphatidylcholine separate from the active site in cobra venom phospholipases A2.

A model structure of Naja naja kaouthia cobra venom phospholipase A2 has been constructed by utilizing molecular modeling techniques. Analysis of the model and available biochemical data reveal the presence in this enzyme of a putative recognition site for choline derivatives in loop 57-70 made up of residues Trp-61, Tyr-63, Phe-64, and Lys-65, together with Glu-55. The magnitude and shape of the electrostatic potential in this binding site are approximately 80% similar to that in the McPC603 antibody binding site specifically recognizing phosphocholine. Docking studies indicate that the recognition site we now describe and the phosphocholine head of an n-alkylphosphocholine molecule are complementary both sterically and electronically, mainly due to anion-cation and cation-pi interactions. Moreover, binding enthalpies of n-heptylphosphocholine to this site are found to parallel the catalytic rate of pancreatic, mutant pancreatic, and cobra venom phospholipase A2 enzymes acting on dihexanoylphosphatidylcholine micelles, suggesting that it behaves as an activator site. This proposal is in keeping with the "dual phospholipid" model put forward to account for the phenomenon of interfacial activation. This novel site is also shown to be able to discriminate choline derivatives from ethanolamine derivatives, in accord with experimental data. On the basis of the results obtained, two functions are assigned to this putative activator site: (i) desolvation of the lipid-enzyme interface, particularly the surroundings of tyrosine at position 69 (Tyr-63), and (ii) opening of the entrance to the active site by means of a conformational change of Tyr-63 whose chi 2 angle rotates nearly 60 degrees.

Amino Acid Sequence

Effect of practice on the voluntary control of a learned breathing pattern.

Changes in orientation of attention and ventilatory data were examined in three normal volunteers who practiced a learned ventilatory pattern over eight training sessions. The breathing task was a voluntary increase of inspiratory duration up to a given target with the aid of informative feedback on this variable. The orientation of attention was investigated through reaction time (RT) to auditory stimuli presented at different points in inspiration and expiration, during either automatic or voluntary control of breathing. Findings show that RTs are longer during voluntary than automatic breathing throughout the experiment, and that they decrease across sessions in both conditions. In the first sessions, RTs were longer during expiration than inspiration but this difference cancels out in the last sessions. The results are discussed in terms of attentional demands of control of breathing, automatization, and the connection between automatic and voluntary control of breathing. This work shows that after eight practice sessions, the orientation of attention displays significant changes; however, the control of breathing remains attention demanding.

Animals

Electromyographic feedback for learning to activate thoracic inspiratory muscles.

The utility of EMG feedback for modifying the muscular pattern of breathing was investigated in twenty-four subjects divided into two groups (feedback, no feedback. Each took part in three 20-min training sessions, 24 h apart. All the subjects were instructed to increase the thoracic contribution of inspired gas. The feedback subjects were shown an EMG signal of the inspiratory muscles of the upper thorax and a signal indicating their current breathing phase (inspiration or expiration). The no feedback subjects only saw the breathing phase signal. The subjects' ability to control muscular activity was assessed as the relative increase in EMG from expiration to the subsequent inspiration. Analysis of variance with group and session as factors showed that feedback subjects performed significantly better, although the improvement in performance over the sessions by the two groups was not significantly different. These results lend some support to the clinical use of EMG feedback in breathing therapy aimed at changing the thoracoabdominal distribution of ventilation. However, further research for improving learning is necessary.

Adult

Unusual foreign bodies in the urethra and bladder.

We report 8 cases of self-inserted unusual foreign bodies in the lower urinary tract, all being treated from 1976 to 1990. Three of them were located in the urethra and 5 in the bladder. Several objects were found (electric cable, tweezers, hairpin, drawing pin, pebbles, paper clip). In 4 cases the objects were inserted for masturbatory purposes. Five of the patients were psychologically ill or handicapped. The most common reason for consultation was dysuria, and the treatment procedures were endoscopy in 5 patients and cystotomy in the other 3.

Adolescent

Assessing attentional control of breathing by reaction time.

The reaction time (RT) to an auditory stimulus was measured in 27 subjects during spontaneous breathing and during controlled breathing, which consisted of maintaining a set inspiratory duration. During spontaneous breathing, reaction times were unrelated to the time the stimulus was delivered during the breathing cycle. During controlled breathing, reaction times were longer than during spontaneous breathing. Peak reaction times were observed at the transition from inspiration to expiration. After the end of controlled breathing, reaction times gradually became shorter until they reached their initial level. The findings are discussed in terms of varying allocation of attentional resources to breathing. It is argued that probe RT methodology provides a suitable means for investigating attentional control of breathing.

Adult

Classical conditioning of ventilatory responses in humans.

A classical conditioning experiment, in which an auditory stimulus was paired with a hypoxic stimulus, was carried out on 34 normal subjects assigned to two groups (experimental and control). Each subject took part in one session divided into two phases, acquisition and test. In the acquisition phase, eight hypoxic and eight auditory stimuli were paired in the experimental group and unpaired in the control group. In the test phase, which was identical for the two groups, the hypoxic stimuli were suppressed and three purely auditory stimuli were presented. Significant differences between the two groups in ventilatory response to these auditory stimuli provided evidence for conditioning. In the control group, no significant changes were elicited by the auditory stimuli, whereas a conditioned increase in total cycle duration was observed in the experimental group. The conditioned response closely resembled the first component of the hypoxic response. Analysis of the pattern of the conditioned response, along with postexperimental interviews, strongly suggests that this response was not mediated by volitional factors.

Acoustic Stimulation

Carcinoma of prostatic ducts.

Carcinoma of prostatic ducts is a rare clinical feature. We have reviewed 398 histories of patients with histologic diagnosis of prostatic carcinoma and found 10 patients with the ductal variety (2.51%). Four had pure ductal transitional cell carcinoma, 5 had mixed acinar adenocarcinoma plus ductal transitional cell carcinoma, and the last one had mixed acinar and ductal adenocarcinoma. Age, symptoms, physical findings, and imaging diagnoses were similar to those of acinar carcinoma. Rectal examination disclosed hard prostate in 9 patients. The metastatic way depended on the histologic elements present in each patient. Cystoscopy showed a malignant-resembling image in 4 cases. The mean survival (23 months) was lower than that of patients with acinar carcinoma. Early diagnosis and radical surgery still are the only way to increase the expectation of life of patients affected by this pathology.

Aged

[Treatment of obstruction caused by prostatic hypertrophy with prazosin. 1-year follow-up].

Since Caine demonstrated the presence of alpha-adrenergic receptors in prostate tissue in 1975, an alpha-blocker capable of producing maximum relaxation of prostatic tissue with minimum side effects has been sought. Prazosin, a selective alpha-1 blocking agent, must meet these requirements. We report the results of a study undertaken in 28 patients with benign hyperplasia of the prostate demonstrated by flowmetry, clinically and by ultrasound. A significant improvement was observed in all patients except for the ultrasound measured prostate size, which remained unchanged. Undesired effects were observed in 36% of the patients. Despite the initial improvement, 89.3% had abandoned treatment at 1 year principally owing to deterioration of the clinical picture and because they were submitted to surgery (the majority) or treatment with other drugs. We can conclude from our results that prazosin is useful for short-term therapy; i.e., until the patient can be referred for surgery.

Aged

Selective chemoprophylaxis guided by multifactorial analysis in superficial bladder cancer.

One hundred and five patients with superficial bladder cancer (60 primary and 45 recurrent tumors) entered a prospective chemoprophylaxis trial after transurethral resection of the tumor. The drug for chemoprophylaxis was chosen by a computer which received the tumor data and analyzed them through a previous program of recurrence risk factors (multivariant analysis). In comparison with the aleatory selection of the drug, this statistical computerized choice has diminished the recurrence index (from 8 to 3) and increased the interval free of disease (from 70 to 83.5 months) in this group of patients.

Antineoplastic Agents

ABO blood groups and bladder carcinoma.

Following some reports concerning the possible influence of ABO blood groups on constitutional types and different features of human pathology, we have investigated if there are relationships between ABO blood groups and bladder tumors. Our findings show that tumoral behavior in patients with bladder carcinoma and blood group O has a tendency to an increased aggressivity with higher tumoral grade and more relapses than what is seen in tumors of patients with A blood group. Although this difference is not statistically significant, we believe that blood group ABO should be considered as a constitutional prognostic factor in bladder carcinoma and further investigations in this field are needed.

ABO Blood-Group System

[Volumetric and structural changes of prostatic carcinoma under hormonal treatment].

The evolution of the ultrasonographic images of 25 patients with advanced carcinoma of the prostate receiving antiandrogen (cyproterone acetate) and LH-RH analogue therapy were studied. Thirteen patients were on daily LH-RH analogue therapy while the remaining patients received a monthly depot dose. At 6 months, the ultrasound follow-up revealed a 20.4% reduction of the transverse and a 19.8% reduction of the anteroposterior diameter for the first patient group. Similar results were observed for the second group comprised of 12 patients who received depot therapy; a mean reduction of the diameters of 119.9% and 18.7%, respectively. At 6 months, 66% of the patients in the first group and 59% of the second group showed an improvement of ultrasound patterns. Infiltration of the seminal vesicles improved for both groups, 41% and 38% of patients, respectively. However, at 12 months this rose to 50% improvement for the group on the daily treatment regimen. The follow-up data after 6 months are as yet unavailable for the group on depot therapy. Transrectal ultrasound is an easy, reproducible method that is very useful in the follow-up of patients with advanced cancer of the prostate receiving hormone therapy.

Aged

Computerized tomography in primary hyperammonemia.

Urea cycle enzymopathies are rare in the literature. They are accompanied by neurological disorders somehow related to the increase in blood ammonia. Reviewing the possible physiopathological course we present a case in which during an eight month period severe cerebral atrophy developed, more intense in the occipital region but totally sparing the posterior cranial fossa structures.

Ammonia

Immunoprophylaxis with Calmette-Guérin bacillus in recurrent superficial bladder tumors.

26 patients with superficial bladder cancer underwent complete removal of tumors by transurethral resection and entered a prospective trial of immunoprophylaxis with Calmette-Guérin bacillus (BCG). The entire group had recurrent tumors that failed to respond to previous prophylaxis with thiotepa (13 patients) or other drugs (13 patients). Intravesical administration of BCG reduced the recurrence index and increased the disease-free interval. Side effects were mild and well tolerated. BCG seems to be effective in the prophylaxis of superficial bladder tumor recurrence after the failure of other drugs.

Administration, Intravesical

[Aztreonam versus tobramycin in acute pyelonephritis. A comparative study].

We performed a comparative study between the monobactam antibiotic aztreonam and the aminoglycoside tobramycin in patients diagnosed as having acute pyelonephritis. The respective doses were 1 gr. IM daily for 7 days, and 100 mgr. IM q 12 h for the same period of time. Clinically, 100% of uncomplicated acute pyelonephritis and 87.5% of complicated infections cured with aztreonam. Tobramycin achieved an 80% cure rate for both types of infections. Microbiologically aztreonam was effective in all uncomplicated acute pyelonephritis, and in 69.56% of the complicated cases (overall microbiological cure rate = 78.7%). The therapeutic failures were ascribable to infections from S. faecalis, an organism naturally resistant to aztreonam. Thus, the microbiological cure rate was 84.2% in complicated pyelonephritis from organisms sensitive to this antimicrobial. The microbiological cure rate for tobramycin was 70% in acute uncomplicated, and 80% in complicated infections. We observed a good clinical and biological tolerance to both antimicrobials. No side effects were observed. Serum and blood biochemical analyses, and coagulation tests revealed no changes.

Acute Disease

Sensitivity of newly established colorectal cell lines to cytotoxic drugs and monoclonal antibody drug conjugates.

A major problem in the chemotherapy of colorectal cancers is their resistance to most cytotoxic drugs which may be due to insufficient cellular transport. Drugs conjugated to monoclonal antibodies recognising tumour antigens may overcome these difficulties by providing access of active agents to the tumour cells. The anti-tumour monoclonal antibody shown to localise in patients with colorectal cancer, 791T/36, has been investigated as a potential targeting antibody. Eight cell lines were established from surgically resected material and were shown to bind 791T/36 antibody. They were screened for their sensitivity to methotrexate, 5-fluorouracil and daunomycin. Although 5-fluorouracil is the drug of choice for chemotherapy of colorectal cancer it was the most cytotoxic drug in only 2 of the 8 cell lines. Only the 4 cell lines which were resistant to methotrexate showed less cytotoxicity with methotrexate than 5-fluorouracil. The cell lines which were resistant to methotrexate were more sensitive to 791T/36-methotrexate conjugates. Daunomycin was the most cytotoxic drug in 4 of the 8 cell lines. However, a similar cytotoxicity was observed for free drug and 791T/36 daunomycin in the two lines tested. Selective monoclonal antibody drug conjugates may offer a solution to treatment of tumours which are resistant to classical chemotherapeutic agents. This is the first report to show that newly established cell lines that are resistant to classical chemotherapeutic agents are rendered sensitive when the drug enters the cell as a drug monoclonal antibody carrier.

Antibodies, Monoclonal