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Biomedical subjects

A Morales

Publications and source records attributed to A Morales.

At least 55 records · Page 3Linked to original sources
PubMed2001

Characterization of a Na+-Ca2+ exchanger NCX1 isoform in bovine fasciculata cells of adrenal gland.

The Na+-Ca2+ exchanger (NCX) is well known to regulate intracellular Ca2+ concentration in many excitable cells. To date, three members of the NCX exchanger gene family have been identified: NCX1, NCX2 and NCX3. In zona fasciculata of the bovine adrenal gland, a Na+-Ca2+ exchanger has been recently found to display biochemical similarities with the NCX1 exchanger of renal basolateral cells. Although a Na+-Ca2+ exchanger has already been characterized in zona medulla of adrenal gland, such an exchanger has never been studied in the adrenal cortex. Thus, we have used a reverse transcriptase-polymerase chain reaction (RT-PCR) assay with specific NCX primers on fasciculata cell cultures. The sequencing of the amplified fragment revealed, for the first time, the presence of a NACA3 isoform of the NCX1 exchanger in the adrenal cortex, similar to the one found in adrenal chromaffin cells and in renal cortex. This isoform is 92 and 94% identical in the portion compared with kidney Na+-Ca2+ exchanger NACA3 of rat and pig, respectively.

Animals↗
PubMed2001

Severe erectile dysfunction is a marker for hyperprolactinemia.

The need for routine prolactin (PRL) measurement in the initial evaluation of erectile dysfunction (ED) has been questioned because of the low rate of hyperprolactinemia (HP) in these men and the costs involved. In addition, it is widely thought that sexual desire problems are a good clinical marker for HP and/or low testosterone in men with ED. Within a 15-month period, 844 consecutive PRL and sexual hormone determinations were conducted in men at the Kingston General Hospital. Of these patients, 138 were comprehensively evaluated at the first visit for ED and completed the International Index of Erectile Function (IIEF). In the 138 patients, 2.2% had severe hyperprolactinemia (>35 ng/ml), within the range of 1-5% previously reported. No correlation between initial prolactin value and the sexual desire domain or the erectile function domain (EFD) of the IIEF was found for this population. However, all cases of severe HP were found to occur in men who scored less than 10 in the EFD of the IIEF. Low libido is widely accepted as a marker of HP. In this study, HP was found in patients not reporting major problems with a desire disorder. Clinically significant HP may be reliably found with routine biochemical evaluation and in this series was not detected in patients with EFD scores above 10. A routine PRL measurement is inexpensive and early detection of a serious and treatable disease may afford greater therapeutic success.

Adult↗
PubMed2001

Apomorphine to Uprima: the development of a practical erectogenic drug: a personal perspective.

The development process for apomorphine SL as an effective treatment for patients with erectile dysfunction has been somewhat unusual. As often is the case, much of the impetus for the basic research originated in academia. However, somewhat unusually, the impetus for early stage clinical research also lay in the hands of the academics. This article represents a historical perspective from one of those involved throughout.

Administration, Oral↗
PubMed2001

Fungemia due to Scedosporium prolificans: a description of two cases with fatal outcome.

Two cases, probably related, of fungemia due to Scedosporium prolificans are described in two patients with acute leukemia. Both were admitted to the hematological ward in nearby rooms, during building work in the hospital. After a previous bacterial sepsis in the neutropenic phase, which improved with antibiotic treatment, the respiratory status in both patients deteriorated presenting acute dypsnea, with a lung infiltrate in one of them. A few hours later both patients died. Blood cultures were positive for S. prolificans. These two new cases of S. prolificans infection stress the importance of awareness of this emerging pathogen in patients who suffer a hematologic malignancy during the neutropenic phase, especially if building work is taking place in the hospital.

Adult↗
PubMed2001

Molecular genetic dissection of the sex-specific and vital functions of the Drosophila melanogaster sex determination gene fruitless.

A multibranched hierarchy of regulatory genes controls all aspects of somatic sexual development in Drosophila melanogaster. One branch of this hierarchy is headed by the fruitless (fru) gene and functions in the central nervous system, where it is necessary for male courtship behavior as well as the differentiation of a male-specific abdominal structure, the muscle of Lawrence (MOL). A preliminary investigation of several of the mutations described here showed that the fru gene also has a sex-nonspecific vital function. The fru gene produces a complex set of transcripts through the use of four promoters and alternative splicing. Only the primary transcripts produced from the most distal (P1) promoter are sex-specifically spliced under direction of the sex-determination hierarchy. We have analyzed eight new fru mutations, created by X-ray mutagenesis and P-element excision, to try to gain insight into the relationship of specific transcript classes to specific fru functions. Males that lack the P1-derived fru transcripts show a complete absence of sexual behavior, but no other defects besides the loss of the MOL. Both males and females that have reduced levels of transcripts from the P3 promoter develop into adults but frequently die after failing to eclose. Analysis of the morphology and behavior of adult escapers showed that P3-encoded functions are required for the proper differentiation and eversion of imaginal discs. Furthermore, the reduction in the size of the neuromuscular junctions on abdominal muscles in these animals suggests that one of fru's sex-nonspecific functions involves general aspects of neuronal differentiation. In mutants that lack all fru transcripts as well as a small number of adjacent genes, animals die at an early pupal stage, indicating that fru's function is required only during late development. Thus, fru functions both in the sex-determination regulatory hierarchy to control male sexual behavior through sex-specific transcripts and sex-nonspecifically to control the development of imaginal discs and motorneuronal synapses during adult development through sex-nonspecific transcript classes.

Alleles↗
PubMed2001

Absorption of alkalized intravesical lidocaine in normal and inflamed bladders: a simple method for improving bladder anesthesia.

PURPOSE: Pharmacokinetic studies have shown that intravesical lidocaine is not sufficiently absorbed by human bladders to achieve significant serum levels and it only provides a superficial local anesthetic effect. We investigated the pharmacokinetics of alkalized intravesical lidocaine in healthy volunteers and patients with interstitial cystitis to determine a safe dose of buffered lidocaine, the effect of interstitial cystitis on lidocaine uptake and the acute local anesthetic effect on bladder pain in interstitial cystitis. MATERIALS AND METHODS: An initial dose finding study was done in 12 healthy volunteers using 4, 5 and 6 mg./kg. 5% lidocaine buffered with 8.4% sodium bicarbonate. Serial lidocaine levels were measured for 3 hours. Serum measurement was repeated in 12 patients with interstitial cystitis using 5 mg/kg. 5% lidocaine with sodium bicarbonate daily for 2 days. Patients rated pain before and during treatment. RESULTS: Healthy volunteers and patients with interstitial cystitis had similar lidocaine absorption profiles with a peak of 1.06 microg/ml. (range 0.66 to 1.71) and 1.3 (range 0.2 to 2.0) at about 30 minutes. Mean pain score in the interstitial cystitis group decreased from a baseline of 6.0 to 1.8 on day 1 and 0.6 on day 2. There were complaints of urethral discomfort after voiding the buffered lidocaine in each group. CONCLUSIONS: Alkalization provides safe and predictable lidocaine absorption into the bladder, as indicated by therapeutic systemic levels in healthy and inflamed bladders. Furthermore, the decrease in acute pain scores in the interstitial cystitis group indicated a concentration of local anesthetic within the bladder wall that was sufficient to block the sensory neurons within the submucosal plexus.

Absorption↗
PubMed2001

Identification and functional analysis of mutations in FAD-binding domain of mitochondrial glycerophosphate dehydrogenase in caucasian patients with type 2 diabetes mellitus.

Ca2+-responsive mitochondrial FAD-linked glycerophosphate dehydrogenase (mGPDH) is a key component of the pancreatic beta-cell glucose-sensing device. The purpose of this study was to examine the association of mutations in the cDNA coding for the FAD-binding domain of mGPDH and to explore the functional consequences of these mutations in vitro. To investigate this association in type 2 diabetes mellitus, we studied a cohort of 168 patients with type 2 diabetes and 179 glucose-tolerant control subjects of Spanish Caucasian origin by single-stranded conformational polymorphism analysis. In vitro site-directed mutagenesis was performed in the mGPDH cDNA sequence to reproduce those mutations that produce amino acid changes in a patient with type 2 diabetes. We detected mutations in the mGPDH FAD-binding domain in a single patient, resulting in a Gly to Arg amino acid change at positions 77, 78, and 81 and a Thr to Pro at position 90. In vitro expression of the mutated constructs in Xenopus oocytes resulted in a significantly lower enzymatic activity than in cells expressing the wild-type form of the enzyme. Our results indicate that although mutations in the mGPDH gene do not appear to have a major role in type 2 diabetes mellitus, the reduction in mGPDH enzymatic activity associated with the newly described mGPDH mutations suggests that they may contribute to the disease in some patients.

Aged↗
PubMed2001

Life cycle and reproductive parameters of Clerada apicicornis signoret (Hemiptera: Lygaeidae) under laboratory conditions.

The life cycle of Clerada apicicornis was determined under laboratory conditions. Mean development times in days were: egg 27.2, nymph I 12.5, nymph II 12, nymph III 13.4, nymph IV 16.4, nymph V 26. The life expectancy of adults ranged from 117 to 317 days (mean 196 days). Based on a cohort of 29 females of C. apicicornis, a horizontal life table was constructed. The following predictive parameters were obtained: net rate of reproduction (Ro = 48.31), intrinsic rate of population increase (r(m) = 0.153), generation time (Tc = 28.20 weeks), and finite rate of population increment (lambda = 1.16). The reproductive value (Vx) for each age class of the cohort females was calculated. The following observed parameters were calculated after mortality in each stage: net rate of reproduction (R'o=13.4), intrinsic rate of population increase (r c' =0.09 ), and finite rate of population increment (lambda' =1.1). The generation time (Tc' =27.4) was estimated using the methods of Laughlin and Bengstron. A vertical life table was elaborated and mortality was described for one generation of the cohort.

Animals↗
PubMed2001

A new continuous cell line from the mosquito Psorophora confinnis (Diptera: Culicidae) and its susceptibility to infections with some arboviruses.

A new cell line, PC-0199-BR, was established from embryonated eggs of the mosquito Psorophora confinnis. To date (September 2000) it has had 62 continuous passages. This is the first report of a cell line of mosquitoes belonging to the genus Psorophora. Cell growth initially was achieved in the MM/VP12 medium, supplemented with 20% fetal bovine serum; however, the subcultures were later adapted to Grace's medium with 10% fetal bovine serum. Cell morphology in the primary cultures was heterogeneous; but later in the established cell line, the predominant cell type was epithelioid. Cultured cells were predominantly diploid (2n=6); however, chromosome abnormalities were observed in a small proportion of the cells in later passages. C and G band patterns were also determined in the karyotype. The cell line isozyme profiles coincided with pupae and adult samples of the species taken from the same colony. A preliminary arbovirus susceptibility study for the cell line was undertaken. No evidence was observed of contamination of the cell line with bacteria, fungi or mycoplasma.

Animals↗
PubMed2001

Andropause--a multisystem disease.

The syndrome of androgen deficiency with aging has important biochemical and clinical manifestations. Whether this is called the andropause or by another name the patients with this condition appear to be suffering an accelerated form of aging and some will have individual or clinical reasons to receive treatment. The changes usually attributed to androgen deficiency have been recognized more recently to be due to a broader problem with a number of interlinked hormonal systems (including growth hormone, IGF-I, melatonin, leptin). Several clinical domains can be identified comprising the andropause: Substance (lean body mass, visceral fat, bone mineral density and hematopoiesis); Surface (hair and skin alterations); Central Nervous System (intellectual capacity, mood and sleep patterns); Sex (desire and erection); Prostate. Investigation is directed at the presenting complaints and measuring the serum bioavailable testosterone. Treatment is currently by testosterone replacement using one of a number of routes (parenteral, oral, transdermal). The object of treatment is improvement in the index clinical domains and biochemical normalization. Contraindications include known or suspected prostate or breast cancer.

Adult↗
PubMed2001

Percutaneous aspiration and sclerotherapy for treatment of spermatoceles.

PURPOSE: Spermatoceles are commonly treated with open surgical ablation. With the increasing shift towards minimally invasive surgery and heightened awareness, both patient and surgeon accept and prefer the less intrusive approach. Treatment of spermatoceles translates into the use of aspiration and sclerotherapy rather than open excision. We report on our prospective study of percutaneous aspiration and sclerotherapy with sodium tetradecyl sulfate for treatment of spermatoceles to determine safety, efficacy and cost-effectiveness. MATERIALS AND METHODS: Patients with symptomatic cystic scrotal lesions were prospectively enrolled in an aspiration and sclerotherapy protocol between October 1998 and June 2000. All patients underwent aspiration followed by sclerotherapy with a sodium tetradecyl sulfate solution. Followup included clinical assessment and scrotal ultrasonography at 12 weeks and on a needed basis thereafter. RESULTS: A total of 28 patients with 34 spermatoceles were enrolled in the protocol. Mean patient age was 61.0 years and mean spermatocele volume was 89.3 ml. Complete followup was available for 31 of 34 (91%) spermatoceles, and the mean duration of followup was 24.6 weeks. Results were cure in 29% success in 36%, partial success in 19% and failure in 16% of cases. Patient satisfaction was 85% and there were no complications. The total cost of each procedure was only $104 (Canadian), and none took more than 10 minutes. CONCLUSIONS: Percutaneous aspiration and sclerotherapy with sodium tetradecyl sulfate is a minimally invasive, simple, safe, inexpensive and reasonably efficacious treatment option for spermatoceles. Initial failures can be salvaged with second treatment.

Adult↗
PubMed2001

cAmp modulates exocytotic kinetics and increases quantal size in chromaffin cells.

The role of cAMP/cAMP-dependent protein kinase (PKA) on the late phase of exocytosis has been studied by amperometry on Ba(2+)-stimulated single bovine chromaffin cells. Forskolin (FSK) increases the intracellular cAMP levels in a concentration-dependent manner. Forskolin (100 nM) does not increase the number of exocytotic events, although it significantly increases the net granule content of catecholamines (CA), which is accompanied by a slowing of the process of degranulation. These effects are reversible, occur within 15 to 60 s, and are not due to newly synthesized CA. Isoprenaline, pituitary adenylate cyclase-activating polypeptide-38 or dB-cAMP reproduce FSK effects as does cholera toxin. The inhibition of phosphodiesterases with 3-isobutyl-1-methylxanthine mimics and potentiates the effect of FSK and isoprenaline. Rolipram and okadaic acid also produce a drastic increase in net granule content of CA, whereas H-89 attenuates the FSK response. These data indicate that cyclic AMP/PKA might favor the granule aggregation before its fusion with cell membrane and slow the late step of the exocytotic process.

Animals↗
PubMed2001

Assessment of long-term patient satisfaction after vesical neck suspension for stress urinary incontinence.

OBJECTIVE: To determine the long-term efficacy of the transvaginal vesical neck suspension in the treatment of stress urinary incontinence in a general uro-gynecology practice. METHODS: The charts of all patients (n = 168) treated at our hospital with a transvaginal technique for vesical neck suspension, over a 5 year period (1990-1995) were reviewed. Only cases with pure, uncomplicated incontinence secondary to increased intra-abdominal pressure as determined by history and physical examination, urodynamics and cystoscopy were considered. The short term (1 month) and long term (> 5 years) results were collated and analyzed. RESULTS: Fifty-one patients were lost for follow-up. The assessment of results was, therefore based on the remaining 117 women (69.6%). The efficacy of the operation (> 90% regain continence or were markedly improved) was confirmed in the short term. The results after 5 years were significantly less optimistic with only 26% of the patients remaining fully continent. However, and additional 41% reported better urinary control beyond 5 years after treatment as compared to their situation prior to surgery. CONCLUSION: The transvaginal vesical neck suspension is an effective, easily performed surgical treatment for simple stress urinary incontinence. It is free of significant complications. The excellent results in the short term, however, decline significantly with a prolonged period of follow-up.

Adult↗
PubMed2001

Mycobacterial cell wall extract for treatment of carcinoma in situ of the bladder.

PURPOSE: Bacillus Calmette-Guerin (BCG) established immunotherapy as an effective modality for carcinoma in situ of the bladder and remains the most effective agent for treatment. However, as a live organism it has the potential for undesirable side effects and toxicity. This result has led to the search for other active and safer biological response modifiers. We investigated the efficacy of a mycobacterial cell wall extract (MCWE) from Mycobacterium phlei, which does not contain live bacteria, for management of carcinoma in situ of the bladder in humans. MATERIALS AND METHODS: The requirement for an emulsified preparation was investigated with photon correlation spectroscopy to determine the stability of the bacterial fragments. A total of 61 patients with histologically documented carcinoma in situ completed the study. Cell wall extract from M. phlei suspended in oil droplets to form an emulsion were instilled into the bladder at a dose of 4 mg. once weekly for 6 weeks and then monthly for 1 year. Response assessment was performed at 3-month intervals. Complete response to treatment indicated the absence of endoscopic and histological evidence of carcinoma in situ. Partial responders were those cases in which cystoscopy and biopsies were negative but cytology was suspicious for malignant cells. All other cases were considered failures. RESULTS: The need for an emulsified suspension of the cell wall extract was confirmed by the demonstration that the cell wall extract alone in urine aggregated, whereas the MCWE emulsion had remained stable. Kaplan-Meier estimates showed negative cystoscopy and biopsies in 62.5% at 12, 49.3% at 24 and 41.1% of patients at 60 weeks after therapy. After this point the number of responders had remained stable. Excellent tolerance with minimal toxicity was observed. CONCLUSIONS: Our study demonstrates clinical activity of low doses of MCWE against human bladder cancer. The results observed at the dosage used in our trial are less than those observed with live BCG. However, MCWE has a better toxicity profile and can be instilled in the presence of a disrupted urothelium. It also appears to exhibit activity in patients in whom BCG has failed.

BCG Vaccine↗