Forebrain-specific ablation of phospholipase Cγ1 causes manic-like behavior.

Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1f/f; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca2+/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1f/f; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.

Deep hypothermic circulatory arrest in adults undergoing aortic surgery: local experience.

INTRODUCTION: The aim of our study was to evaluate the efficacy and safety of deep hypothermic circulatory arrest (DHCA) as a method of cerebral protection during aortic surgery. MATERIALS AND METHODS: We carried out a retrospective review of 59 consecutive patients (48 men, 11 women) undergoing elective or emergency aortic surgery requiring DHCA from January 1999 to April 2002 in 2 tertiary care hospitals. Data regarding demographics, clinical characteristics, operation type, duration of circulatory arrest, nasopharyngeal temperatures, use of retrograde cerebral perfusion and central nervous system (CNS) morbidity and perioperative mortality were collected and analysed. RESULTS: There were 47 (79.7 %) operations for aortic dissections and 12 (20.3 %) for aortic aneurysms. The mean duration of circulatory arrest was 42 +/- 23 minutes. The lowest nasopharyngeal temperature at the time of arrest was 16.5 degrees +/- 1.9 degrees C. Eight (13.6 %) patients had a new irreversible neurologic deficit postoperatively. These patients had a mean circulatory arrest time of 50 +/- 28 minutes. Temporary neurologic dysfunction occurred in 8 (13.6 %) patients. Intra-hospital mortality was 22 %. The mean circulatory arrest time for patients who died was 54 +/- 24 minutes. CONCLUSION: DHCA is a simple and effective method of CNS protection in aortic surgery with satisfactory outcomes. With increased surgical and anaesthetic experience, as well as selective use of adjuncts of cerebral protection, reductions in mortality and neurological morbidity will likely be achieved in the future.

Optimizing of gadolinium-enhanced MR angiography by manipulation of acquisition and scan delay times.

An optimized protocol for achieving high-quality contrast-enhanced MR angiography (CE MRA) was designed and evaluated. Time-intensity curves of the test bolus and main bolus were compared in 11 volunteers. To identify the acquisition zone sensitive to venous overprojection, sequential filling phantoms which consisted of 12 test tubes were developed and scanned. Using the parameters of the time-intensity curve which were consistent between the test and main boluses and the parameters of the sensitive acquisition zone in the pulse sequences, the protocol for calculation of scan delay time and acquisition time was optimized. The new protocol was verified by comparison of lower extremity CE MRAs acquired by traditional (scan delay time = peak enhancement time minus injection duration/2 + acquisition time/2; n = 12) and new (n = 23) protocols. The arterial and venous enhancing times of the time-intensity curves of the test and main boluses were statistically consistent (p < 0.01). The length of the sensitive acquisition zone was one-half the acquisition duration. With the parameters identified in the time-intensity curve and pulse sequence analyses, a new protocol was developed. For validation, the new protocol was able to study the smaller arteries such as the distal tibial arteries and branches of the femoral and iliac arteries (p < 0.01). Using the optimized protocol, higher-quality images were obtained than those acquired by traditional methods.

Prevalence of malocclusion among Latino adolescents.

Although numerous studies have documented malocclusion in various ethnic groups in the United States, the prevalence of malocclusion in the Latino population is not well known. The Latino population may be the largest minority group in the United States by the year 2004. This study analyzes the occlusion of 507 Latino adolescents between the ages of 12 and 18 years. More than 93% of the subjects demonstrated some form of malocclusion. The distribution of malocclusion patterns is presented and contrasted with data published for other ethnic groups. Information about the prevalence and types of malocclusion in the Latino population should be of interest to general dental practitioners and specialists.

The human B1 bradykinin receptor exhibits high ligand-independent, constitutive activity. Roles of residues in the fourth intracellular and third transmembrane domains.

The B1 bradykinin (BK) receptor (B1R) is a seven-transmembrane domain, G protein-coupled receptor that is induced by injury and important in inflammation and nociception. Here, we show that the human B1R exhibits a high level of ligand-independent, constitutive activity. Constitutive activity was identified by the increase in basal cellular phosphoinositide hydrolysis as a function of the density of the receptors in transiently transfected HEK293 cells. Several B1R peptide antagonists were neutral antagonists or very weakly efficacious inverse agonists. Constitutive B1R activity was further increased by alanine mutation of Asn(121) in the third transmembrane domain of the receptor (B1A(121)). This mutant resembled the agonist-preferred receptor state since it also exhibited increased agonist affinity and decreased agonist responsiveness. A dramatic loss of constitutive activity occurred when the fourth intracellular C-terminal domain (IC-IV) of the human B2 BK receptor subtype (B2R), which exhibits minimal constitutive activity, was substituted in either B1R or B1A(121) to make B1(B2ICIV) and B1(B2ICIV)A(121), respectively. Activity was partially recovered by subsequent alanine mutation of a cluster of two serines and two threonines in IC-IV of either B1(B2ICIV) or B1(B2ICIV)A(121), a cluster that is important for B2R desensitization. The ligand-independent, constitutive activity of B1R therefore depends on epitopes in both transmembrane and intracellular domains. We propose that the activity is primarily due to the lack of critical epitopes in IC-IV that regulate such activity.

Transcaval TIPS in patients with failed revision of occluded previous TIPS.

OBJECTIVE: To determine the feasibility of transcaval transjugular intrahepatic portosystemic shunt (TIPS) in patients with occluded previous TIPS. MATERIALS AND METHODS: Between February 1996 and December 2000 we performed five transcaval TIPS procedures in four patients with recurrent gastric cardiac variceal bleeding. All four had occluded TIPS, which was between the hepatic and portal vein. The interval between initial TIPS placement and revisional procedures with transcaval TIPS varied between three and 31 months; one patient underwent transcaval TIPS twice, with a 31-month interval. After revision of the occluded shunt failed, direct cavoportal puncture at the retrohepatic segment of the IVC was attempted. RESULTS: Transcaval TIPS placement was technically successful in all cases. In three, tractography revealed slight leakage of contrast materials into hepatic subcapsular or subdiaphragmatic pericaval space. There was no evidence of propagation of extravasated contrast materials through the retroperitoneal space or spillage into the peritoneal space. After the tract was dilated by a bare stent, no patient experienced trans-stent bleeding and no serious procedure-related complications occurred. After successful shunt creation, variceal bleeding ceased in all patients. CONCLUSION: Transcaval TIPS placement is an effective and safe alternative treatment in patients with occluded previous TIPS and no hepatic veins suitable for new TIPS.

Osteoma cutis coexisting with cutis laxa-like pseudoxanthoma elasticum.

Pseudoxanthoma elasticum (PXE) is a heritable disorder of elastic fibers characterized by yellowish, coalescing papules on the loose and wrinkled flexural area. There have been no reports of osteoma cutis associated with PXE. A 17-year-old Korean girl presented cutis laxa-like marked wrinkling on the flexural area, and a skin biopsy specimen revealed multiple foci of ossification with irregularly clumped, basophilic-stained elastic fibers in the reticular dermis and calcium deposits along the elastic fibers. Ultrasonographic evaluation showed multiple tiny osteomas diffusely scattered along the entire abdominal wall, axillae, and medial aspect of the upper arms. We report the first case of osteoma cutis coexisting with cutis laxa-like PXE.

Lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens.

We describe a case of lichen planus pemphigoides with circulating autoantibodies against 200 and 180 kDa epidermal antigens. A 24-year-old man presented pruritic erythematous patches with occasional central blister formation on the face, neck, and trunk and erythematous hyperkeratotic patches on the elbows and feet for 10 months. Histopathological findings of the neck and plantar lesions were consistent with lichen planus. Direct immunofluorescence studies from both lesions showed a linear deposition of IgG and C3 and cytoid bodies along the basement membrane zone. Indirect immunofluorescence studies demonstrated circulating IgG antibodies deposited on the epidermal side of salt-split skin. Immunoblot analysis using epidermal extract showed that the patient's serum reacted with 180 kDa bullous pemphigoid antigen (BPAG2) and a 200 kDa antigen. The cutaneous lesions almost cleared with a low dose of prednisolone and acitretin.

Segmental and subsegmental pulmonary arteries: evaluation with electron-beam versus spiral CT.

PURPOSE: To compare contrast agent-enhanced spiral and electron-beam computed tomography (CT) for the analysis of segmental and subsegmental pulmonary arteries. MATERIALS AND METHODS: CT angiography of the pulmonary arteries was performed in 56 patients to rule out pulmonary embolism. Electron-beam CT was performed in 28 patients. The other 28 patients underwent spiral CT with comparable scanning protocols. The depiction of segmental and subsegmental arteries was analyzed by three independent readers. The contrast enhancement in the main pulmonary artery was measured in each patient. RESULTS: Analysis was performed in 1,120 segmental and 2, 240 subsegmental arteries. One segmental (RA7, P =.010) and two subsegmental (LA7b, P =.029; RA6a+b, P =.038) arteries in paracardiac and basal segments of the lung were depicted significantly better with electron-beam CT. There was no statistically significant difference between electron-beam and spiral CT in the total number of analyzable peripheral arteries depicted. The mean contrast enhancement in the main pulmonary artery was 362 HU in electron-beam CT studies versus 248 HU in spiral CT studies. CONCLUSION: Detailed visualization of peripheral pulmonary arteries is well within the scope of advanced CT techniques. Electron-beam CT has minor advantages in analyzing paracardiac arteries, probably because of reduction of motion artifacts and higher contrast enhancement. Further studies are needed to establish whether electron-beam CT allows a more confident diagnosis of emboli in these vessels.

Contrast-enhanced magnetic resonance angiography: dose the test dose bolus represent the main dose bolus accurately?

OBJECTIVE: To determine whether the time-intensity curves acquired by test and main dose contrast injections for MR angiography are similar. MATERIALS AND METHODS: In 11 patients, repeated contrast-enhanced 2D-turbo-FLASH scans with 1-sec interval were obtained. Both test and main dose time intensity curves were acquired from the abdominal aorta, and the parameters of time-intensity curves for the test and main boluses were compared. The parameters used were arterial and venous enhancement times, arterial peak enhancement time, arteriovenous circulation time, enhancement duration and enhancement expansion ratio. RESULTS: Between the main and test boluses, arterial and venous enhancement times and arteriovenous circulation time showed statistically significant correlation (p < 0.01), with correlation coefficients of 0.95, 0.92 and 0.98 respectively. Although the enhancement duration was definitely greater than infusion time, reasonable measurement of the end enhancement point in the main bolus was impossible. CONCLUSION: Only arterial and venous enhancement times and arteriovenous circulation time of the main bolus could be predicted from the test-bolus results. The use of these reliable parameters would lead to improvements in the scan timing method for MR angiography.

The optimization of scan timing for contrast-enhanced magnetic resonance angiography.

OBJECTIVE: To determine the optimal scan timing for contrast-enhanced magnetic resonance angiography and to evaluate a new timing method based on the arteriovenous circulation time. MATERIALS AND METHODS: Eighty-nine contrast-enhanced magnetic resonance angiographic examinations were performed mainly in the extremities. A 1.5T scanner with a 3-D turbo-FLASH sequence was used, and during each study, two consecutive arterial phases and one venous phase were acquired. Scan delay time was calculated from the time-intensity curve by the traditional (n = 48) and/or the new (n = 41) method. This latter was based on arteriovenous circulation time rather than peak arterial enhancement time, as used in the traditional method. The numbers of first-phase images showing a properly enhanced arterial phase were compared between the two methods. RESULTS: Mean scan delay time was 5.4 sec longer with the new method than with the traditional. Properly enhanced first-phase images were found in 65% of cases (31/48) using the traditional timing method, and 95% (39/41) using the new method. When cases in which there was mismatch between the target vessel and the time-intensity curve acquisition site are excluded, erroneous acquisition occurred in seven cases with the traditional method, but in none with the new method. CONCLUSION: The calculation of scan delay time on the basis of arteriovenous circulation time provides better timing for arterial phase acquisition than the traditional method.

Common blue naevus with satellite lesions: possible perivascular dissemination resulting in a clinical resemblance to malignant melanoma.

We report a case of common blue naevus with polymorphous guttate and linear satellite lesions, thereby mimicking peripherally spreading malignant melanoma. Histopathologic examination showed that the naevus cells are clustered around blood vessels in the primary as well as satellite lesions, suggestive of spreading of the naevus cells along the perivascular space. Such biological behaviour resulting in a clinical manifestation of a malignant melanoma-like lesion is a rarity in common blue naevus, a benign cutaneous disorder that is devoid of a malignant potential, and has not been described before.

Regulation of type I collagen and interstitial collagenase mRNA expression in human dermal fibroblasts by colchicine and D-penicillamine.

Sclerosis is a disease process in which idiopathic hardening occurs in the skin and/or internal organs as a result of the accumulation of type I collagen, induced mainly by transforming growth factor-beta. Colchicine and D-penicillamine are widely used for its treatment. Their effects are known to be due to post-translational down-regulation of type I collagen synthesis, with colchicine also up-regulating interstitial collagenase. To determine whether or not they have any pre-translational effect on type I collagen and MMP-1, and also to observe their effects on the action of TGF-beta, cultured neonatal foreskin fibroblasts were treated with colchicine and D-penicillamine, singly and together. The amount of type I collagen and MMP-1 mRNA were quantitated by Northern blot hybridization. Colchicine suppresses the basal level of type I collagen mRNA but minimally stimulates the mRNA expression of MMP-1, whereas D-penicillamine does not have any significant effects on either. Colchicine was also able to significantly suppress the TGF-beta-induced up-regulation of type I collagen mRNA expression.

Septic arthritis versus transient synovitis at MR imaging: preliminary assessment with signal intensity alterations in bone marrow.

PURPOSE: To find any differential magnetic resonance (MR) imaging findings between septic arthritis and transient synovitis in pediatric patients. MATERIALS AND METHODS: The MR imaging findings in nine pediatric patients with septic arthritis and 14 with transient synovitis were retrospectively studied. The diagnoses were made by means of joint aspiration with bacteriologic study, arthrotomy, and clinical evaluation. MR imaging findings were analyzed with emphasis on the grade of joint effusion and alterations in signal intensity in the soft tissue and bone marrow of the affected hip joint. RESULTS: Signal intensity alterations in bone marrow (i.e., low signal intensity on fat-suppressed gadolinium-enhanced T1-weighted spin-echo images and high signal intensity on fat-suppressed T2-weighted fast spin-echo images) were seen in eight of nine patients with septic arthritis. These signal intensity alterations consisted of mild juxtaarticular changes in six patients without osteomyelitis and extensive changes in the femoral head and neck in two patients with coexistent osteomyelitis. Signal intensity alterations in bone marrow were not seen in the 14 patients with transient synovitis. CONCLUSION: Signal intensity alterations in the bone marrow of the affected hip joint are useful in the differentiation of septic arthritis from transient synovitis.

Surveillance for asthma--United States, 1960-1995.

PROBLEM/CONDITION: Asthma is one of the most common chronic diseases in the United States, and it has increased in importance during the preceding 20 years. Despite its importance, no comprehensive surveillance system has been established that measures asthma trends at the state or local level. REPORTING PERIOD: This report summarizes and reviews national data for specific end-points: self-reported asthma prevalence (1980-1994), asthma office visits (1975-1995), asthma emergency room visits (1992-1995), asthma hospitalizations (1979-1994), and asthma deaths (1960-1995). DESCRIPTION OF SYSTEM: The National Center for Health Statistics (NCHS) annually conducts the National Health Interview Survey, which asks about self-reported asthma in a subset of the sample. NCHS collects physician office visit data with the National Ambulatory Medical Care Survey, emergency room visit data with the National Hospital Ambulatory Medical Care Survey, and hospitalization data with the National Hospital Discharge Survey. NCHS also collects mortality data annually from each state and produces computerized files from these data. We used these datasets to determine self-reported asthma prevalence, asthma office visits, asthma emergency room visits, asthma hospitalizations, and asthma deaths nationwide and in four geographic regions of the United States (i.e., Northeast, Midwest, South, and West). RESULTS: We found an increase in self-reported asthma prevalence rates and asthma death rates in recent years both nationally and regionally. Asthma hospitalization rates have increased in some regions and decreased in others. At the state level, only death data are available for asthma; death rates varied substantially among states within the same region. INTERPRETATION: Both asthma prevalence rates and asthma death rates are increasing nationally. Available surveillance information are inadequate for fully assessing asthma trends at the state or local level. Implementation of better state and local surveillance can increase understanding of this disease and contribute to more effective treatment and prevention strategies.