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Biomedical subjects

A Alexander

Publications and source records attributed to A Alexander.

At least 37 records · Page 2Linked to original sources

Prostate imaging may not be necessary in nonpalpable carcinoma of the prostate.

OBJECTIVES: Stage T1c carcinoma of the prostate is defined as a nonpalpable carcinoma (NPC-P) that is not visible by imaging and is identified by needle biopsy performed because of elevated prostate-specific antigen (PSA) concentrations. The purpose of this study was to define the incidence of normal findings on transrectal ultrasound (TRUS) and/or endorectal coil magnetic resonance imaging (EMRI) among patients with NPC-P, as well as to investigate the value of differentiating patients with Stage T1c disease from all other patients with NPC-P. METHODS: The records of 2211 patients diagnosed with prostate carcinoma between 1988 and 1995 were reviewed to identify 291 men with NPC-P. TRUS and EMRI reports were analyzed with regard to the presence and laterality of hypoechoic nodules or low-signal areas reported on T2-weighted images, respectively. Ninety percent of patients (n = 262) had at least six prostate biopsies, 185 patients (64%) underwent both TRUS and EMRI, 224 (77%) had TRUS, and 251 (86%) had an EMRI study. RESULTS: Results were considered normal in 101 (47%) of 214 patients undergoing TRUS, in 58 (23%) of 249 undergoing EMRI, and in 22 (12%) of 185 undergoing both TRUS and EMRI. For the side of the prostate with positive biopsy results, correlation with imaging abnormalities was better for EMRI than for TRUS (39% versus 24%). There was no significant difference in mean PSA value, distribution of Gleason score, or unilateral versus bilateral positive biopsy results among patients with normal versus abnormal findings on both TRUS and EMRI. CONCLUSIONS: (1) Only 12% of men with NPC-P have no TRUS or EMRI abnormalities, fulfilling the criteria for Stage T1c prostate carcinoma. (2) Those patients with Stage T1c disease do not differ from patients with NPC-P up-staged by TRUS or EMRI, with regard to pretreatment PSA levels, Gleason scores, and the probability of having bilateral rather than unilateral positive biopsy results. (3) The value of classifying patients with NPC-P into Stage T1c versus higher stages of prostate carcinoma on the basis of imaging should be questioned.

Adenocarcinoma↗

Increased hepatic Na,K-ATPase activity during hepatic regeneration is associated with induction of the beta1-subunit and expression on the bile canalicular domain.

Cellular and molecular mechanisms regulating the activity of the sodium pump or Na,K-ATPase during proliferation of hepatocytes following 70% liver resection have not been defined. Na,K-ATPase may be regulated by synthesis of its alpha- and beta-subunits, by sorting to either the sinusoidal or apical plasma membrane domains, or by increasing membrane lipid fluidity. This study investigated the time course of changes during hepatic regeneration for Na, K-ATPase activity, lipid composition and fluidity, and protein content of liver plasma membrane subfractions. As early as 4 h after hepatic resection, Na,K-ATPase activity was increased selectively in the bile canalicular fraction. It reached a new steady state at 12 h and remained elevated for 2 days. Although hepatic regeneration was associated with a reduced cholesterol/phospholipid molar ratio and increased fluidity, measured with two different probes, these changes in lipid metabolism were in the sinusoidal membrane domain. The Na,K-ATPase beta1-subunit, but not the alpha1-subunit, was increased selectively at the bile canalicular surface as shown by immunoblotting of liver plasma membrane subfractions and the morphological demonstration at both the light and electron microscopic levels. Furthermore, cycloheximide blocked the rise in beta1-subunit mRNA levels. Since the time course for beta1-subunit accumulation was similar to that for activation of Na,K-ATPase activity, this change implicated the beta1-subunit in activating sodium pump activity.

Animals↗

Paraorbital lesions.

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Central Nervous System Neoplasms↗

Location of the descending palatine artery in relation to the Le Fort I osteotomy.

PURPOSE: This study evaluated the positional relationship of the descending palatine artery to the Le Fort I osteotomy. MATERIALS AND METHODS: Three separate examinations were performed. In the first, 30 human skulls were used, and measurements were made of the greater palatine canal and foramen in relation to maxillary landmarks pertaining to the Le Fort I osteotomy. In the second, 40 patients with normal or minimal sinus mucosal thickening were selected from a pool of patients who underwent computed tomography (CT) scanning for sinus evaluation. These patients were scanned on a Somatome Plus spiral CT scanner as part of a routine sinus protocol, with the addition of an axial image 3 mm above the nasal floor where the Le Fort I osteotomy is usually performed. The distance from the greater palatine canal to the piriform rim was measured. In the third, eight fresh cadavers were used, and the distance from the internal maxillary artery to the nasal floor was measured. RESULTS: The internal maxillary artery enters the pterygopalatine fossa approximately 16.6 mm above the nasal floor and gives off the descending palatine artery. The descending palatine artery travels a short distance within the pterygopalatine fossa and then enters the greater palatine canal. It travels approximately 10 mm within the canal in an inferior, anterior, and slightly medial direction to exit the greater palatine foramen in the region of the second and third molars. CONCLUSION: Injury to the descending palatine artery during Le Fort I osteotomy can be minimized by not extending the osteotomy more than 30 mm posterior to the piriform rim in females. This distance can be extended to 35 mm in males. Pterygomaxillary separation should be made by closely adapting the cutting edge of a curved osteotome or right-angled saw to the pterygomaxillary fissure while avoiding excessive anterior angulation. Furthermore, the superior cutting edge of the osteotome or saw blade should be less than 10 mm above the nasal floor.

Adolescent↗

Management and referral patterns of epilepsy in india.

Evaluation of management and referral pattern is very important in the organization of medical services for epilepsy. In order to study the management and referral pattern of epilepsy, a structured questionnaire was administered to 100 epilepsy patients attending a referral hospital in Kerala State, India. Of these, 61.4% of them were living in villages; 65% had a monthly income less than Rs. 1000. Seventy-five percent of the patients had generalized seizures. The mean delay in diagnosis was more for those from villages (13.5 months) as compared to those from urban areas (6.4 months) and for women (11.7 months) as compared to men (7.8 months). Previous consultation before referral to this Institute included general practitioners (61%), specialists (50%) and neurologist or neurosurgeon (27%). Eighty-eight patients have had EEG and 51 patients have had CT Scans. Thirty-nine per cent of patients required hospitalization for control of seizures that was significantly (P = 0.036) higher among those living in an urban area. Seventy-five per cent of patients were collecting drugs from private pharmacies. No patient was collecting antiepileptic drugs from government institutions even though such a facility was available within 5 km of their residence. This study has revealed that the organization and delivery of neurological services for epilepsy leaves much to be desired.

Adolescent↗

The effect of dexamethasone, cyclosporine, and rapamycin on T-lymphocyte proliferation in vitro: comparison of cells from patients with glucocorticoid-sensitive and glucocorticoid-resistant chronic asthma.

Inhibition of T-lymphocyte activation may provide a useful approach to the treatment of chronic severe asthma. We compared rapamycin, a novel immunosuppressive drug, with cyclosporine and dexamethasone for its effects in inhibiting proliferation of T lymphocytes from patients with glucocorticoid-resistant and glucocorticoid-sensitive asthma. Phytohemagglutinin-stimulated peripheral blood T lymphocytes from 11 patients with clinically glucocorticoid-resistant and 8 patients with glucocorticoid-sensitive chronic asthma were tested for sensitivity to these drugs in a highly reproducible proliferation assay. All drugs inhibited proliferation in a dose-dependent manner (10(-6) to 10(-10) mol/L). T lymphocytes from the patients with glucocorticoid-resistant asthma were significantly less sensitive (p < 0.01) to dexamethasone than those of patients with glucocorticoid-sensitive asthma over a wide concentration range. In contrast, cyclosporine and rapamycin inhibited cells from both patient groups to an equivalent extent. The presence of exogenous interleukin-2 abrogated the inhibitory effect of dexamethasone but not that of cyclosporine or rapamycin, suggesting that dexamethasone may act principally by inhibition of interleukin-2 production, whereas the latter drugs exert distinct or additional inhibitory effects. Stimulation of peripheral blood T lymphocytes with phytohemagglutinin for 24 hours before addition of the drugs abolished the inhibitory effect of dexamethasone and significantly reduced that of cyclosporine. The inhibitory effect of rapamycin was, however, unaltered. These data suggest that dexamethasone and cyclosporine exert their effects only at an early stage of T-lymphocyte activation, whereas rapamycin is able to inhibit lymphoblasts. The fact that the inhibitory mechanisms of these drugs are different might explain why cyclosporine and rapamycin are effective in inhibiting T lymphocytes from both patients with glucocorticoid-sensitive and those with glucocorticoid-resistant asthma. The data further suggest that cyclosporine and rapamycin may be effective for the therapy of glucocorticoid-resistant asthma.

Adult↗

Distribution of the matrix metalloproteinases stromelysin, gelatinases A and B, and collagenase in Crohn's disease and normal intestine.

AIMS: To investigate the role of the matrix metalloproteinases (MMPs) in the connective tissue changes seen in the intestine in Crohn's disease. METHODS: Indirect immunofluorescence microscopy using specific antibodies to the MMPs (collagenase, gelatinase A and B, and stromelysin) were used to assess the distribution of these enzymes in normal and diseased intestine. RESULTS: In normal intestine the matrix metalloproteinases were confined to a few isolated inflammatory cells, but in Crohn's disease, the inflammatory infiltrate was associated with increased numbers of polymorphonuclear leucocytes which stained positive for gelatinase B. Stromelysin was also detected extracellularly on the connective tissue matrix in regions of smooth muscle cell proliferation and mucosal degradation. Interestingly, in ulcerative colitis, another inflammatory bowel disease, stromelysin was localised in the lamina propria in regions of mucosal loss. CONCLUSIONS: The increased numbers of inflammatory cells containing gelatinase B, and the localisation of extracellular stromelysin in regions of fibrosis and mucosal degradation, suggest that these enzymes have a role in the pathological changes seen in Crohn's disease. In cases of ulcerative colitis stromelysin was also detected on the lamina propria in regions of mucosal loss, and seems to be associated with the connective tissue changes that precede mucosal loss.

Colitis, Ulcerative↗

Toluene abuse: physical basis for hypointensity of the basal ganglia on T2-weighted MR images.

PURPOSE: To explain the hypointensity in the basal ganglia on T2-weighted magnetic resonance (MR) images of brains of toluene abusers. MATERIALS AND METHODS: Eight patients with histories of toluene abuse underwent MR imaging. A bilayered model of dipalmitoylphosphatidylcholine (DPPC; 100 mmol/L concentration) and varying concentrations of toluene was formed. The DPPC control and toluene-mixed bilayers underwent MR imaging. T1 and T2 were measured as a function of toluene and lipid concentrations. RESULTS: T2-weighted images of patients who had abused toluene showed marked hypointensity in the thalami and moderate hypointensity in the basal ganglia. Measurements of the DPPC-toluene phantom indicated that toluene-tainted lipid bilayers dramatically shortened T2 and had little effect on T1. By comparison, DPPC itself had little discernible effect on either T1 or T2. CONCLUSION: This model suggests that partitioning of toluene into the lipid membranes of cells in cerebral tissue may be responsible for the hypointensity of basal ganglia noted on T2-weighted MR images of brains of toluene abusers.

Adult↗

Mammalian PC-12 cell genetically engineered for human cytochrome P450 2E1 expression.

The stable expression of the human cytochrome CYP2E1 (P450 alcohol) was performed in the mammalian cell line PC-12. This cell line expressed cytochrome b5 (58 +/- 12 pmol/mg microsomal protein vs 528 +/- 80 pmol/mg in microsomal human liver) and a high level of NADPH: cytochrome P450 reductase (140 +/- 20 nmol.min-1.mg microsomal protein-1 vs 68 +/- 48 nmol.min-1.mg-1 in microsomal human liver). An expression plasmid was constructed using the cDNA for the human CYP2E1 mRNA and the Rous sarcoma virus (RSV) promoter. This plasmid was co-transfected with the plasmid RSVneo into PC-12 cells. Clones were selected for resistance to the neomycin analog, G418, and then screened for expression of the CYP2E1 isozyme by testing for 6-hydroxylation of chlorzoxazone, a specific substrate for CYP2E1. Expression of CYP2E1 was confirmed in one clone, DB-7, by Western blot analysis and by measurement of monooxygenase activities which were not detectable in PC-12 cells. Chlorzoxazone 6-hydroxylation, n-butanol oxidation and dimethylnitrosamine N-demethylation were localized in microsomes (62, 60 and 63 pmol.min-1.mg microsomal protein-1, respectively) and were inhibited by carbon monoxide and diethyldithiocarbamate, both inhibitors of P450 enzymes. Although the level of the enzyme activities was about a tenth of that measured in human liver microsomes, CYP2E1 expressed in DB-7 cells has catalytic competence similar to human liver CYP2E1. DB-7 cells metabolized acetaminophen and this metabolic activation was shown to be toxic to these cells by release of lactate dehydrogenase. Construction of recombinant cell lines expressing CYP2E1 provides a useful tool for studying the catalytic properties of this enzyme and the consequent cytotoxic effects of substrates metabolized by this enzyme.

1-Butanol↗

Effects of genotype and cryopreservation of avian semen on fertility and number of perivitelline spermatozoa.

1. The fertility of freshly diluted and cryopreserved samples of semen obtained from a population of chickens selected for duration of fertility of cryopreserved spermatozoa (FS line) and its unselected control (FC line) were compared over a range of spermatozoa concentrations (10, 40, 80, and 160 x 10(6) sperm/50 microliters insemination). 2. The spermatozoa of the FS line had greater fertility than spermatozoa of the FC line, whether freshly diluted or cryopreserved. Cryopreservation resulted in a reduction in fertility, regardless of line. There were no significant line by genotype interactions. 3. There were fewer spermatozoa from the FC line than the FS line found in the perivitelline membrane (perivitelline spermatozoa). The increase in number of perivitelline spermatozoa with increasing sperm concentration was greater in the FS than FC line. However, the slope of the increase in sperm number in the perivitelline membrane with increasing concentrations of cryopreserved spermatozoa was zero. 4. A minimum of 10(3) perivitelline spermatozoa must be found on day 2 post-insemination for duration of fertility to exceed three days. The ability to produce spermatozoa capable of reaching the forming perivitelline membrane appears to be a quantitative, rather than a qualitative, trait and may be subject to genetic manipulation.

Animals↗

Distribution of adenylate cyclase and GTP-binding proteins in hepatic plasma membranes.

Hepatic membrane subfractions prepared from control rats demonstrated forskolin (FSK)-stimulated adenylate cyclase activity in the basolateral (sinusoidal) but not apical (canalicular) plasma membrane. After bile duct ligation (BDL) for 12 or 24 h, there was an increase in FSK-stimulated adenylate cyclase activity in the apical membrane (54.2 +/- 3.9 pmol.mg-1 x min-1). The mechanism for this increase was explored further. ATP hydrolysis was found to be much higher in the apical than the basolateral membrane. Increasing the ATP levels in the assay enhanced apical membrane adenylate cyclase activity (10.5 +/- 0.2 pmol.mg-l.min-1); however, total adenosinetriphosphatase (ATPase) activity was not altered after BDL. Extraction of the apical membrane with bile acids or other detergents resulted in a two- to threefold increase in adenylate cyclase activity (30.6 +/- 3.6 pmol.mg-1 x min-1; detergent C12E8) This suggested that bile duct ligation was acting via the detergent-like action of bile acids to uncover latent adenylate cyclase activity on apical membranes. Further studies demonstrated that both BDL and detergent extraction also enhanced toxin-directed ADP-ribosylation of Gs alpha (cholera toxin) and Gi alpha (pertussis toxin) in the apical but not the basolateral membrane. After BDL, Gi alpha was found to be twofold greater in the apical membrane than the basolateral membrane. Immunoblotting using specific G protein antibodies further confirmed that apical membranes from control rats had a higher concentration of Gi1, 2 alpha and beta and slightly elevated levels of Gi3 alpha and Gs alpha compared with the basolateral membrane. The results demonstrate that adenylate cyclase and heterotrimeric GTP-binding proteins are present on the apical membrane, but measurement of their functional activity requires detergent permeabilization of apical membrane vesicles and is limited by the presence of high ATPase activity.

Adenosine Triphosphatases↗

Requirement for three membrane-spanning alpha-helices in the post-translational insertion of a thylakoid membrane protein.

The insertion of a protein into a lipid bilayer usually involves a short signal sequence and can occur either during or after translation. A light-harvesting chlorophyll a/b-binding protein (LHCP) is synthesized in the cytoplasm of plant cells as a precursor and is post-translationally imported into chloroplasts where it subsequently inserts into the thylakoid membrane. Only mature LHCP is required for insertion into the thylakoid. To define which sequences of the mature protein are necessary and sufficient for thylakoid integration, fusion and deletion proteins and proteins with internal rearrangements were synthesized and incubated with isolated thylakoids and stroma. No evidence is found for the existence of a short signal sequence within LHCP, and, with the exception of the amino terminus and a short lumenal loop, the entire mature protein with consecutively ordered alpha-helices is required for insertion into thylakoid membranes. The addition of positive charges into stromal but not lumenal segments permits the insertion of mutant LHCPs into isolated thylakoids. Replacement of the LHCP transit peptide with the transit peptide from plastocyanin has no effect on LHCP insertion and does not restore insertion of the lumenal charge addition mutants.

Base Sequence↗

Fine-needle aspiration of a periurethral Teflon-filled cyst following radical prostatectomy.

Periurethral Teflon injections are being used increasingly for the treatment of urinary incontinence after radical prostatectomy. We report a case of a man who developed increasing obstructive urinary symptoms and stress incontinence following radical retropubic prostatectomy. Six months earlier, he had undergone periurethral Teflon injections. On transrectal ultrasound and magnetic resonance imaging, a 3.2-cm cystic lesion was noted at the prostatic bed near the bladder neck where the Teflon had been injected. Ultrasound-guided transperineal fine-needle aspiration of the cyst yielded a specimen with numerous birefringent crystalline Teflon particles. Although previous reports have described granulomatous tissue reaction, no multinucleated giant cells were present to suggest granuloma formation. To our knowledge, this is the first reported case of Teflon cyst formation following periurethral Teflon injections. The patient's history, imaging studies, cytopathology, and review of the literature are presented in this report.

Aged↗

Arthroscopic surgery of the knee: its role in the support of U.S. troops during Operation Desert Shield on USNS mercy.

The role of arthroscopy in the preconflict deployment of a large number of military troops is not well defined. Between September 1990 and January 1991, while deployed to the Persian Gulf for Operation Desert Shield 73 patients underwent on-board elective arthroscopy on the USNS Mercy. There were 71 men and two women with an average age of 27 years (range 19-47). Indications for arthroscopy included clinical diagnosis of meniscus tear, acute hemarthrosis, chronic effusion, and intra-articular loose body. Findings at the time of arthroscopy included 34 patients (47%) with meniscus tears; 17 (23%) with anterior cruciate ligament tears; five (7%) with isolated grade II-IV chondromalacia involving the patella, trochlea, femoral condyles, or tibial plateaus; six (8%) with synovitis; four (5%) with osteochondritis dissecans of the medial femoral condyle; two (3%) with a medial retinacular tear secondary to patella dislocation; and 10 (14%) with normal arthroscopic examinations. Forty-nine patients (66%) were returned to duty at an average of 6 days postoperatively, obviating the need to evacuate these patients from the Middle East theatre.

Adult↗

Treatment of iatrogenic femoral artery injuries with ultrasound-guided compression.

Iatrogenic injuries of the groin are becoming more common after increasingly sophisticated vascular intervention. These injuries are accurately detected by duplex and color Doppler ultrasonography. Recent treatment of these lesions by ultrasound-guided compression repair (UGCR) has been described. During a 1-year period we identified 18 femoral artery injuries, including 17 pseudoaneurysms and one arteriovenous fistula. Three of the pseudoaneurysms thrombosed spontaneously before attempted treatment. The remaining 15 lesions underwent a trial of UGCR. Successful closure was accomplished in 10 patients (56%). Seven of these lesions were successfully treated during the initial session, and thrombosis was accomplished after repeat compression in three additional lesions. Three patients who were given anticoagulants had a failed UGCR, but their pseudoaneurysms thrombosed after administration of anticoagulants was discontinued. Two patients had failed UGCR and required operation. Seven (88%) of eight patients who were not given anticoagulants were successfully treated. In contrast only two (29%) of seven patients given therapeutic doses of anticoagulant medication were successfully treated by the technique. There was no statistical difference between mean pseudoaneurysm diameter, mean width and length of pseudoaneurysm neck, or depth of pseudoaneurysm neck from skin surface in patients in whom successful initial closure was achieved when compared with those patients in whom the initial attempt failed. UGCR is a safe, simple, noninvasive technique that can be used to treat many femoral artery injuries that traditionally were treated with surgery. The technique can be applied by any laboratory that has the necessary ultrasonography equipment and is currently the method of choice for treating uncomplicated iatrogenic femoral artery injuries at our institution.

Adult↗

Ablation of osteoid osteomas with a percutaneously placed electrode: a new procedure.

Osteoid osteoma is a benign, self-limited tumor of bone that usually requires surgical excision for relief of pain and to prevent long-term consequences. Radio-frequency electrodes have been successfully and safely used to ablate small areas of the central nervous system and to perform ablation elsewhere in the body. The authors have used this technique in four patients with proved or presumptive osteoid osteoma, completely relieving the symptoms in three.

Adult↗

Endoluminal sonography of the urinary tract: preliminary observations.

Endoluminal sonography of the urinary tract was performed by using endoluminal ultrasound transducers contained within 2-mm-diameter catheters. The catheters were inserted into the urinary bladder via the urethra and advanced into the ureters and renal pelvis under cystoscopic control; then, cross-sectional images of the bladder, ureters, and renal pelvis were obtained. Two dogs and seven human patients were studied. In one dog, a 4.5-mm pseudopolyp, which was surgically created in the bladder wall, was successfully imaged; in the other, stones 2 mm or larger inserted into the bladder were identified. Of the seven patients, sonography showed stones embedded in the renal parenchyma (one patient) and the mucosa of the distal ureter (one patient). These were ultimately confirmed by their eventual removal. In a third, sonography showed a tumor of the distal ureter and identified the depth of the tumor. This was confirmed by biopsy. In a fourth, sonography clearly showed a crossing vessel as the cause for narrowing of the proximal ureter. In a fifth, sonography showed that the cause of a ureteral stricture was idiopathic. In the last two cases, sonography did not reveal a cause for hematuria. In these last three cases, negative sonographic results were confirmed by direct ureteroscopic examinations and follow-up studies. Our observations based on this limited study suggest that endoluminal sonography is a useful procedure for diagnosing diseases of the urinary tract. Further study is warranted.

Adult↗