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PubMed1993

Obtaining a family psychiatric history: is it worth the effort?

The purpose of this study was to determine whether, for first-degree relatives of patients presenting to a mood disorders clinic, family history information on psychiatric conditions collected by a psychiatrist and incorporated into the patient's medical records is as informative as that gathered during an interview specifically designed to collect family history data. The study group consisted of 472 first-degree relatives of 78 randomly selected index cases from a large mood disorders genetic database. Family history of psychiatric disorders recorded in regular psychiatric medical records ("clinician history"), and data obtained by a genetic counsellor administering specific family psychiatric history questionnaires to patients and multiple family informants ("family history") were compared using a kappa statistic. Good agreement between the two methods on the presence or absence of a psychiatric disorder was found among first-degree relatives of index cases, but poor agreement was found with respect to the presence or absence of a specific mood disorder diagnosis(es) in a relative. The results suggest that a clinician-generated family psychiatric history is sensitive to the presence or absence of a psychiatric disorder when compared to a more structured detailed genetic interview. However, for research purposes, a clinician-generated family psychiatric history of a specific mood disorder diagnosis, without supporting collateral information, may not be reliable for use in supporting a mood disorder diagnosis in a patient and/or his relatives.

Adult↗
PubMed2001

Three-dimensional portography using multislice helical CT is clinically useful for management of gastric fundic varices.

OBJECTIVE: This study seeks to evaluate three-dimensional (3D) helical CT portography as a tool for examining patients with gastric fundic varices. SUBJECTS AND METHODS: We compared 3D helical CT portography and conventional angiographic portography in 30 consecutive patients with gastric fundic varices. We assessed whether 3D helical CT portography is useful in selecting patients and in evaluating the results of balloon-occluded retrograde transvenous obliteration. RESULTS: Three-dimensional helical CT portography simultaneously depicted second or third branches of the intrahepatic portal vein and provided images of entire portosystemic collaterals. On 3D helical CT portography, gastric fundic varices were seen in 30 patients (100%), left gastric veins in 19 (63%), posterior gastric veins or short gastric veins in 28 (93%), gastrorenal shunts in 27 (90%), paraumbilical veins in three (10%), and inferior phrenic veins in two patients (7%). Findings of 3D helical CT portography and conventional angiographic portography were in close agreement. However, in four patients, posterior gastric veins or short gastric veins were not seen on conventional angiographic portography images of the spleen, but they were clearly revealed on 3D helical CT portography. Treatment was successful in all patients except one. Three-dimensional helical CT portography could easily evaluate therapeutic results. CONCLUSION: Three-dimensional helical CT portography proved so effective that it can be considered a less invasive alternative than conventional angiographic portography in assessing portosystemic collaterals. CT portography is useful in selecting candidates from patients with gastric fundic varices for retrograde transvenous obliteration and also in evaluating therapeutic results.

Adult↗
PubMed1996

Protection of mammalian cells against chloroethylating agent toxicity by an O6-benzylguanine-resistant mutant of human O6-alkylguanine-DNA alkyltransferase.

Low levels of expression in haemopoietic cells of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (A Tase), is associated with the dose-limiting sensitivity of these cells to the chemotherapeutic chloroethylating and related methylating agents. Thus, the use of agents which deplete ATase such as O6-benzylguanine (O6-beG), as a tumour sensitisation strategy is likely further to potentiate collateral toxicity in bone marrow. In order to address this problem, we have engineered two mutants of human ATase (hAT) for resistance to O6-beG and characterised the in vitro properties of the proteins. In one mutant protein (hATPA), the proline at position 140 was changed to an alanine, whilst in the other (hATPA/GA) an additional mutation (glycine 156 to alanine) was also introduced. The I50 values for O6-beG of hAT, hATPA and hATPA/GA are 0.16, 2.5 and > 500 microM respectively, indicating that hATPA is resistant and hATPA/GA effectively refractory to O6-beG inactivation. Both mutant proteins retain comparable methyl transfer kinetics to those of nonmutant hAT and although they are thermally less stable in vitro than the wild-type protein, both can be substantially stabilised by DNA. Expression of either hAT or hATPA/GA following gene transfer into RJKO cells, raised the D37 value for mitozolomide from 0.35 microgram/ml for control cells to 10 micrograms/ml in the absence of O6-beG. However, whilst hAT-mediated protection was ablated by 20 microM O6-beG, the hATPA/GA protein provided protection against mitozolomide under the same conditions. Similar observations were made with chlorozotocin. The data suggest that transfer and expression of O6-beG resistant ATase in normal progenitor cells, should be a useful therapeutic strategy to protect the cells from the cytotoxic effects of the O6-alkylating agents even when used in combination with tumour sensitising agents such as O6-beG.

Animals↗
PubMed1990

[The diagnosis of deep venous thrombosis of the lower extremities using high-resolution real-time and CW-Doppler sonography. Accuracy and limitations].

The combination of high-resolution real time and continuous wave (CW) Doppler sonography is particularly valuable for the detection of venous thrombosis in the lower limbs. A total of 235 venous sonograms were prospectively compared with phlebography (gold standard) and indicated a sensitivity and specificity of 93%-100% and 96%-99%, respectively, depending on the thrombosis site. The positive and negative predictive values ranged between 90% and 97% and 97% and 100%, respectively. The value of real-time venous sonography, which basically entails assessing venous compressibility for the exclusion of thrombosis, is limited in the presence of small non-occlusive thrombi by the elasticity of the surrounding anatomic structures and the sonographic visibility of the veins. It is also evident that partial thrombosis in readily visualized veins (e.g., the inguinal region) is more obvious with sonography than phlebography. In addition, the proximal end of acute, extensive thrombus with poor collateral circulation is better visualized by sonography.

Adolescent↗
PubMedDate not supplied

[Validating the Simpson-Angus Extrapyramidal Collateral Symptom Evaluation Scale].

OBJECTIVES: The study was aimed at validating the Simpson-Angus scale for neuroleptic-induced extrapyramidal syndrome in Colombia, using a Spanish version of the scale. METHODS: The scale was validated in four steps: translating the scale, pilot study, preliminary use for factorial analysis and analysis of validity, reliability and sensitivity to change. RESULTS: Factorial structure and internal consistency were evaluated in 86 psychiatric inpatients. Test-retest and inter-rater reliability were evaluated in a 15-patient subgroup. Concurrent validity was analysed by simultaneously applying Simpson-Angus and Chouinard scales. Sensitivity to change was evaluated by comparing the scores of two different clinical points in a 20-patient subgroup. Main factor analysis revealed that the scale has a one-dimensional structure; the Glabella tap did not contribute towards total variability of the condition measured for the scale. Test-retest and inter-rater reliability values, concurrent validity and sensitivity to change were good. Correlation estimation scores were above 0.8 and accuracy levels were also good. CONCLUSIONS: The Spanish version of the SA scale, adapted for this study, is suitable for assessing neuroleptic-induced extrapyramidal syndrome; it would be a useful instrument in both clinical practice and research settings in Colombia. However, an important limitation could be its lack of detecting any domain different to that of rigidity.

Adolescent↗
PubMed2001

Clinical and angiographic correlates of dobutamine-induced wall motion patterns after myocardial infarction.

The ability of different dobutamine-induced wall motion patterns to define the anatomic status of the infarct-related artery (IRA) was evaluated in 159 patients who underwent dobutamine stress echocardiography (DSE) and coronary angiography 10 +/- 2 and 18 +/- 3 days, respectively, after hospital admission. The DSE result was classified as: (1) biphasic: improvement with a low dose followed by deterioration with a high dose; (2) worsening: direct deterioration at low or high doses; (3) sustained improvement: improvement with a low dose that was maintained at high dose; and (4) no change: no change during the entire protocol. A diameter narrowing >70% (50% for the left main stem) of major coronary arteries indicated a severe lesion. Angiograms were classified according to the jeopardy score and collateral circulation graded according to Rentrop's classification. DSE was positive in 92 patients (22 had biphasic results and 70 had worsening results) and negative in 67 patients (14 had sustained improvement and 53 had no changes). Biphasic response was associated with more frequent anterior infarction (p <0.05) and higher resting (p <0.001) and peak (p <0.01) wall motion score indexes. The IRA was totally occluded in 4 of the 92 patients (4%) with positive (worsening pattern) and 12 of the 67 patients (18%) with negative (no change pattern) tests. The biphasic pattern was associated with the highest jeopardy score and was significantly (p <0.05) more specific (100%) compared with worsening (78%) in identifying a severe stenosis of the IRA. The combination of ischemic patterns provided a significantly superior sensitivity (p <0.0001). Logistic regression analysis identified the biphasic pattern as the only significant predictor. Conversely, the prediction of total occlusion of the IRA was poor. Sustained improvement was the most specific (100%) predictor of absence of severe stenosis of the IRA, whereas the combination with no change pattern provided a significantly superior sensitivity (p <0.0001). Thus, DSE effectively predicts the residual stenosis of the IRA. In particular, the biphasic response has an excellent specificity and positive predictive value and is the only significant predictor among clinical and echocardiographic variables.

Adrenergic beta-Agonists↗
PubMed1996

Chemoprotection of normal tissues by transfer of drug resistance genes.

The effectiveness of many types of antitumour agent is limited by (i) acute dose limiting cytotoxicity, principally myelosuppression but also lung, liver and gastrointestinal tract toxicity, (ii) the risk of therapy related secondary malignancy and (iii) the inherent or acquired drug-resistance of tumour cells. As the management of the acute toxic effects improve, the more insidious effects, and particularly haematological malignancies, are anticipated to increase. Furthermore, attempts to overcome tumour cell resistance to treatment can lead to increased collateral damage in normal tissues. One approach to circumventing both the acute toxic and chronic carcinogenic effects of chemotherapy would be to use gene therapy to achieve high levels of expression of drug resistance proteins in otherwise drug-sensitive tissues. To date the products of the multi-drug resistance (MDR-1) and the human O6-alkylguanine-DNA-alkyltransferase (ATase) gene have been used in preclinical experiments to demonstrate proof of principle, and the former of these is now being tested in a clinical situation. Here we discuss the potential of drug-resistance gene therapy to provide chemoprotection to normal tissues and examine the prospects for a dual approach which combines this with pharmacological sensitisation of tumours to chemotherapeutic agents.

ATP-Binding Cassette Transporters↗
PubMed1998

Elbow arthrography.

Elbow arthrography provides useful information that is not available with noninvasive imaging. This article describes normal elbow anatomy as seen by arthrography. Technical aspects of arthrography with regard to radiographs and CT and MR imaging are reviewed. Indications for MR arthrography include identification of loose bodies, chondral and osteochondral fractures, collateral ligament tears, and synovial and capsular abnormalities.

Arthrography↗
PubMed1986

Noninvasive diagnosis of renal artery stenosis by ultrasonic duplex scanning.

We retrospectively studied the results of duplex scanning for evaluation of renal artery disease in 158 patients. Satisfactory examinations were achieved in 144 patients (90%). Arteriograms were available for 43 renal arteries. We used the ratio of the peak velocities in the renal artery and the aorta (RAR) to separate nonstenotic arteries (less than 60% diameter reduction) from stenotic arteries (greater than 60% diameter reduction). With an RAR of greater than 3.5 to indicate stenotic lesions, duplex scanning had a sensitivity of 91% (20 of 22 diseased arteries correctly identified) and specificity of 95% (20 of 21 normal or insignificantly diseased arteries correctly identified). One of four occluded arteries was incorrectly interpreted as patent because of misidentification of a collateral vessel. Prospective studies will be necessary to validate this test and establish other criteria for a more detailed classification of renal artery stenosis. The ratio of the end-diastolic to peak systolic velocities in the renal artery (EDR) tended to decrease with increasing serum creatinine levels, presumably because renal vascular resistance increases with end-stage parenchymal disease. EDR may prove useful in the detection of advanced parenchymal disease before renal artery revascularization is attempted.

Aorta, Abdominal↗
PubMed2001

Sensitization of human tumor cells to CPT-11 via adenoviral-mediated delivery of a rabbit liver carboxylesterase.

Irinotecan, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is activated by carboxylesterases (CE) to yield the potent topoisomerase I inhibitor, SN-38. We have demonstrated previously that a rabbit liver CE is approximately 100-1000-fold more efficient at drug activation than a highly homologous human CE. In an attempt to use rabbit CE expression in combination with CPT-11 for gene therapy approaches for the treatment of cancer, we have developed an adenoviral vector expressing this intracellular CE. After transduction, this virus produces very high levels of CE activity in a panel of human tumor cell lines and results in marked sensitization to CPT-11 of all of the transduced cells. Reductions in IC(50) values for this drug ranged from 11-127-fold. Additionally, comparison with an adenovirus expressing a secreted form of the rabbit CE indicated that a collateral effect could be achieved with reductions in the IC(50) values ranging from 4-19-fold. These data suggest that the described reagents may be suitable for use in vivo in a viral-directed enzyme prodrug therapy approach using CPT-11.

Adenoviridae↗
PubMed2002

The assessment of pancreatic exocrine function by bentiromide test in patients with chronic portal vein thrombosis.

INTRODUCTION: It has been noted in the literature that cavernous transformation of the portal vein (CTPV) can cause pancreatic duct atrophy, probably by enhanced collateral formation, but the clinical significance of this has not been established. AIMS: To evaluate whether CTPV affects the pancreatic exocrine functions. METHODOLOGY: Eighteen patients with CTPV were identified and prospectively studied. In these cases, despite a full clinical, biochemical, radiologic, and hematological evaluation, we found no etiologic factor for thrombosis in the portal vein (PV). All patients underwent a detailed evaluation for pancreatic morphology and pancreatic exocrine functions. In all cases, abdominal Doppler ultrasonography (US), abdominal spiral computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) were performed for evaluation of pancreatic morphology. For the purpose of this study, serial biochemical tests, including measurement of serum amylase, pancreatic amylase, lipase, glucose, calcium, and lipids, were performed every 3 months. All 18 patients also underwent a bentiromide test to determine whether there was any exocrine pancreatic insufficiency. The findings were compared with those for 20 healthy control subjects and reference controls. RESULTS: For all 18 patients with idiopathic CTPV and all controls, ERCP was performed successfully. The pancreatic duct was determined to be smaller than in control subjects and in a reference control group ( < 0.05). In this group serum pancreatic amylase, alkaline phosphatase, and direct bilirubin levels were found to be higher than in controls, and statistically important differences between the two groups ( < 0.05) were documented. In all 18 subjects the bentiromide test was well tolerated and was performed successfully. For 15 of them (83%), we found that urinary excretion of para-amino benzoic acid (PABA) was significantly less than in control subjects and the reference control group ( < 0.05). CONCLUSION: Pancreatic duct atrophy in patients with CTPV is clinically significant. When clinical signs are not manifest and routine biochemical tests are not useful for detecting exocrine pancreatic insufficiency, the bentiromide test is highly sensitive and specific for detecting probable pancreatic insufficiency in patients with CTPV.

4-Aminobenzoic Acid↗
PubMed2004

Mesostriatal and mesolimbic projections of midbrain neurons immunoreactive for estrogen receptor beta or androgen receptors in rats.

The dopamine (DA) inputs to the caudate putamen, the nucleus accumbens, and the amygdala in rats are sensitive to circulating estrogens and androgens. One mechanism for the hormone modulation of these systems may be via actions at cognate intracellular estrogen and androgen receptors. However, although it is known that specific subsets of midbrain DA neurons are immunopositive for estrogen receptor beta (ERbeta) or androgen receptors (ARs), it is not known where these receptor-bearing cells project. To address this issue, we combined double-label immunocytochemistry with retrograde tract tracing to identify the forebrain projections of ERbeta- or AR-immunoreactive (IR) midbrain neurons. Specifically, Fluoro-Gold and/or cholera toxin were injected into discrete subregions of the caudate-putamen, the nucleus accumbens, or the amygdala. Evaluations of the resultant midbrain labeling revealed that ERbeta-IR neurons sent collateral projections mainly to both the ventral caudate-putamen and the amygdala, but not to the dorsal caudate or nucleus accumbens. In contrast, AR-IR neurons projected either to the amygdala or the nucleus accumbens but not to the caudate-putamen. The organization of these forebrain projections concurs with some of the known hormone sensitivities of mesostriatal and mesolimbic DA systems in rats and provides an anatomical model that predicts separate influences for androgens and estrogens over mesostriatal and mesolimbic DA systems.

Amygdala↗
PubMedDate not supplied

Evaluation of cerebrovascular disease by combined extracranial and transcranial Doppler sonography. Experience in 1,039 patients.

Results from 1,039 combined cervical and transcranial Doppler examinations are reported. Satisfactory transcranial signals were not found in 2.7% of the cases. Compared with angiography, the accuracy of transcranial criteria in assessing collateral flow over the circle of Willis was 94 and 88% for anterior and posterior circulation, respectively. The method also appeared very promising for detection of lesions of the intracranial arteries although the number of such cases with angiographic verification was limited in the present series. Arterial narrowing due to cerebral vasospasm was diagnosed with a sensitivity of 80%. In patients with ruptured intracranial aneurysms, an incidence of 93% arterial narrowing in basal cerebral arteries was found. Patients with subarachnoid hemorrhage and no aneurysm on angiography also showed arterial narrowing with an incidence of 56%. It was possible to monitor the time course and severity of cerebral vasospasm. Arteriovenous malformations were characterized by Doppler findings of high velocities and low pulsatilities. These lesions were diagnosed with an accuracy of 95%.

Cerebral Angiography↗
PubMedDate not supplied

The magnetic resonance imaging appearance of individual structures of the posterolateral knee. A prospective study of normal knees and knees with surgically verified grade III injuries.

The purpose of this study was to contrast the magnetic resonance imaging appearance of uninjured components of the posterolateral knee with that of injured structures, and to assess the accuracy of magnetic resonance imaging in identifying posterolateral knee complex injuries. Thin-slice coronal oblique T1-weighted images through the entire fibular head were used to identify the posterolateral structures in seven uninjured knees. The appearance of corresponding grade III injuries to these structures was identified prospectively in 20 patients and verified at the time of surgical reconstruction. The sensitivity, specificity, and accuracy of imaging for the most frequently injured posterolateral knee structures in this series were as follows: iliotibial band-deep layer (91.7%, 100%, and 95%), short head of the biceps femoris-direct arm (81.3%, 100%, and 85%), short head of the biceps femoris-anterior arm (92.9%, 100%, and 95%), midthird lateral capsular ligament-meniscotibial (93.8%, 100%, and 95%), fibular collateral ligament (94.4%, 100%, and 95%), popliteus origin on femur (93.3%, 80%, and 90%), popliteofibular ligament (68.8%, 66.7%, and 68%), and the fabellofibular ligament (85.7%, 85.7%, and 85.7%). Magnetic resonance imaging of the knee was accurate in the identification of these injuries.

Humans↗
PubMed2005

Use of a force-plate actometer for detecting and quantifying vertical leaping induced by amphetamine in BALB/cJ mice, but not in C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ, and CD-1 mice.

The force-plate actometer is a relatively new computer-based instrument with high temporal and spatial resolution that has been used to measure the behavioral effects of genetic restriction (e.g., inbred mice) and drugs (e.g., dopaminergic agonists and antagonists) on a variety of behaviors in rodents, including locomotor activity, stereotypies, tremor, and wall rearing. In the present study, the force-plate actometer was used to measure the differential effects of amphetamine-induced (10.0mg/kg) vertical leaping in five inbred mouse strains (BALB/cJ, C57BL/6J, DBA/2J, 129X1/SvJ, and C3H/HeJ) and one outbred stock (CD-1). Across a 13-day, five-injection procedure, mice of the BALB/cJ strain leaped an average of 82 times per 60-min session; the C57BL/6J, DBA/2J, 129X1/SvJ, C3H/HeJ strains and CD-1 stock always showed zero or near zero levels of vertical leaping following amphetamine treatment. The quantitative precision afforded by the force-plate actometer revealed that the mean duration of the leaps by the BALB/cJ strain was 0.18 second, and the corresponding peak force averaged 87.4 gram per leap, which was more than 400% of the average body weight of this strain. Although no evidence of behavioral sensitization was indicated for amphetamine's effects on vertical leaping, sensitization to amphetamine's effects on spatial confinement (i.e., bouts of low mobility) was observed in all mouse types. Results indicate that the force-plate actometer is an instrument well suited for detecting and quantifying both vertical leaping and collateral behaviors induced by amphetamine in mice.

Amphetamine↗
PubMed2006

MRI and CT diagnosis of acute desmopathy of the lateral collateral sesmoidean (navicular) ligament and long-term outcome in a horse.

Clinical, magnetic resonance imaging (MRI) and computed tomography (CT) findings of acute desmopathy of the lateral collateral sesmoidean (navicular) ligament (CSL) in a 13-year-old Hanoverian mare are presented. On admission to the clinic the horse showed a grade 5/6 left front-limb lameness at the walk, pain on coffin joint manipulation, and coffin joint effusion. Despite a positive palmar digital nerve block, radiographs and ultrasonography did not indicate reasons for the severe clinical signs. However, MRI revealed damage to the CSL and bone marrow oedema of the navicular bone (NB), whereas a focal bone defect of the NB at the CSL insertion zone was demonstrated best by CT. The horse was managed with complete box rest and a fibreglass cast for four weeks followed by a controlled exercise program. Follow-up examination revealed no lameness at the trot three months later and the patient had fully recovered within six months.

Animals↗
PubMed2001

Lipopolysaccharide inhibits induction of long-term potentiation and depression in the rat hippocampal CA1 area.

We examined the effects of lipopolysaccharide, a bacterial endotoxin, on synaptic plasticity in the rat hippocampal CA1 area in vitro. Lipopolysaccharide suppressed the induction of long-term potentiation elicited by tetanic stimulation and long-term depression, elicited by low-frequency stimulation of Schaffer collateral-commissural fibres at 10 and 50 microg/ml, respectively. Lipid A (1 microg/ml), the biologically active component of lipopolysaccharide, mimicked the effects of 10 microg/ml lipopolysaccharide on long-term potentiation and depression. Nifedipine, an L-type voltage-sensitive Ca(2+) channel antagonist, did not influence the induction of long-term potentiation and depression, whereas a high concentration of extracellular calcium enabled long-term potentiation induction in the presence of 10 microg/ml lipopolysaccharide. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 50 microM), nifedipine (10 microM) or lipopolysaccharide (10 or 50 microg/ml) partially reduced the magnitude of tetraethylammonium-induced long-term potentiation. Nifedipine combined with lipopolysaccharide completely blocked tetraethylammonium-induced long-term potentiation. Whole-cell voltage clamp recordings showed that lipopolysaccharide suppressed NMDA receptor-mediated excitatory postsynaptic currents (EPSCs). Our results indicate that lipopolysaccharide acutely modifies synaptic plasticity by blocking Ca(2+) entry through NMDA receptors, suggesting a possible mechanism for the amnesic action of bacterial infection.

Animals↗