Comparison of manual compression, Z-stitch, and suture-mediated vascular closure device techniques in dogs undergoing percutaneous transvenous intervention.

INTRODUCTION/OBJECTIVES: Manual compression has been standard of care for maintaining hemostasis after percutaneous endovascular intervention, but can be time-consuming and associated with vascular complications. Alternative closure methods include the figure-of-eight suture (Z-stitch) and vascular closure device (VCD) techniques. We hypothesized that compared to manual compression, Z-stitch and VCD would significantly reduce time-to-hemostasis after transvenous access, and the proportion of dogs with vascular patency would not differ significantly among treatments. ANIMALS: Forty-six client-owned dogs undergoing percutaneous transvenous interventional procedures. MATERIALS AND METHODS: Dogs with vessel diameter <5 mm were randomized to undergo manual compression or Z-stitch, while those with vessel diameter ≥5 mm were randomized to undergo manual compression, Z-stitch, or VCD. Time-to-hemostasis, bleeding scores, presence of vascular patency one day and two to three months post-procedure, and complications were recorded. Data are presented as median (95% confidence interval). RESULTS: In all 46 dogs, the right external jugular vein was used. Time-to-hemostasis was significantly shorter in the Z-stitch (2.1 [1.8-2.9] minutes) compared to VCD (8.6 [6.1-11.8] minutes; P<0.001) and manual compression (10.0 [10.0-20.0] minutes; P<0.001) groups. Time-to-hemostasis was significantly shorter in the VCD vs. manual compression (P=0.027) group. Bleeding scores were significantly greater at 5 and 10 min (P<0.001 and 0.013, respectively) in manual compression, compared to Z-stitch group. There was no difference in the proportion of dogs with vascular patency between groups (P=0.59). CONCLUSIONS: Z-stitch and VCD are effective venous hemostasis methods after percutaneous transvenous intervention, with Z-stitch providing the most rapid time-to-hemostasis. Both Z-stitch and VCD techniques have low complication rates and effectively maintain vascular patency.

Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats.

INTRODUCTION/OBJECTIVES: The objective of this study was to describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. ANIMALS: Six adult purpose-bred cats MATERIALS AND METHODS: Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a two-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 h for two weeks. Blood samples were collected at predetermined time points for 48 h postdose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). RESULTS: Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89 mL/min/kg) and 2175.56 mL/kg (1961-2341.57 mL/kg), respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 µg/mL (0.45-1.17 µg/mL) and 1.5 h (0.5-4 h) after a single oral dose (2 mg/kg), and 2.29 µg/mL (1.91-2.48 µg/mL) and 1.0 h (0.5-1.5 h) with chronic oral dosing (3 mg/kg), respectively. Elimination half-life was 2.75 h (2.52-4.10 h) and 4.29 h (3.33-5.53 h) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. CONCLUSIONS: Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good to excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.

Comparative transcatheter occlusion of patent ductus arteriosus: multicenter collaborative study across pediatric and veterinary cardiology centers.

INTRODUCTION/OBJECTIVE: Transcatheter therapeutics have revolutionized treatment of patent ductus arteriosus (PDA). Greater understanding of corrective interventions across species can advance best practices, protocols, and outcomes while minimizing adverse events. The objective of this study was to describe characteristics and outcomes in children and dogs undergoing transcatheter PDA occlusion. ANIMALS, MATERIALS AND METHODS: This was a multicenter, retrospective cohort study from two pediatric and three veterinary centers. Demographics, procedural characteristics, and outcomes were assessed. RESULTS: Data included 202 children and 106 dogs treated from July 2019 to June 2021. Forty-five (23%) children and 19 (18%) dogs had congestive heart failure prior to catheterization. Transvenous and transarterial approaches for deployment were most used in children and dogs, respectively. All children had percutaneous vascular access compared to 17 (16%) dogs. Intraprocedural anticoagulation was standard for children (100% of 165 reported), but not for dogs (2/103). The median (interquartile range) pulmonary ostium diameter in children was 2.2 mm (1.5-3.0 mm) and 3.0 mm (2.0-4.2 mm) in dogs when all body sizes were considered (P<0.001). Amplatzer™ Duct Occluder was most commonly used in children (64/202, 32%); the Amplatz® Canine Duct Occluder was used in dogs (96/100, 96%). Closure was manual compression in all children, whereas vessel ligation was most used in dogs (74/104, 73%). Successful device deployment was achieved in 197 (98%) children and 98 (93%) dogs (P=0.03). Major reasons for failure included device embolization in six (2.9%) children and PDA morphology concerns in four (3.8%) dogs. CONCLUSIONS: Transcatheter PDA occlusion is successful in children and dogs. Study data might be useful for optimizing transcatheter therapeutics and animal models for interventional cardiology.

Transcatheter closure of patent ductus arteriosus in 11 dogs and one cat after incomplete or aborted surgical ligation.

OBJECTIVE: To describe the characteristics and outcomes of transcatheter patent ductus arteriosus (PDA) occlusion after incomplete or aborted surgical ligation in dogs and cats. ANIMALS: Twelve client-owned animals (11 dogs and one cat). MATERIALS AND METHODS: This retrospective study describes data from animals with aborted or incomplete surgical PDA ligation that subsequently underwent transcatheter closure using endovascular methods. Patient demographics, reason for incomplete or aborted surgery, complications, and method of transcatheter occlusion were recorded. Data are presented as mean ± standard deviation or median (interquartile range), where appropriate. RESULTS: For all cases, median age at surgery was 12.2 months (4.9-15.1 months) and at catheterization was 15.4 months (8.9-21.9 months), with 79 days (29-209 days) between surgical and interventional procedures. Median weight at catheterization was 4.5 kg (2.5-12.6 kg). Reasons for failed surgical ligation included hemorrhage during ductal dissection in seven dogs, residual flow in four dogs, and inability to identify the ductus in one cat. Transcatheter closure was successfully performed using a canine duct occluder in eight dogs, transarterial coil embolization in two dogs, and transvenous coil embolization in one dog and one cat. Metallic hemoclips partially obscured angiographic findings in three cases with prior surgical hemorrhage but did not prevent transcatheter closure. In all cases, ductal flow was successfully attenuated, with no or trace residual shunting on angiography and complete occlusion the following day on echocardiography. CONCLUSIONS: When surgery is unsuccessful, either owing to hemorrhage or residual flow, transcatheter closure of PDA is feasible, even in small patients.

Outcomes after combined percutaneous balloon valvuloplasty and external beam radiation therapy for the treatment of congenital pulmonic stenosis in four dogs.

Valve restenosis after percutaneous balloon pulmonary valvuloplasty (BPV) for the treatment of congenital pulmonic stenosis (PS) may occur in up to 17% of canine cases. Outcomes in dogs with PS that are treated with repeat BPV after restenosis have not been described. The present report details the clinical courses of four dogs with congenital PS, previously treated with conventional BPV and atenolol (n = 4) or atenolol alone (n = 1), two with anomalous, circumpulmonary coronary artery anatomy, which underwent BPV followed immediately by external beam radiation therapy (BPV + EBRT) to prevent valve restenosis. External beam radiation therapy involved five daily fractions of 3.6 Gray to the pulmonic valve. Echocardiographic and clinical follow-up information for 2-4 years after BPV + EBRT is presented. Three dogs experienced long-term reduction in transpulmonic pressure gradient. In one dog, which was treated with conservative BPV + EBRT as first-line therapy, return of transpulmonic pressure gradient to pretreatment levels was noted by 7 months after BPV + EBRT. Although clinical benefit remains unproven, the addition of EBRT to conventional BPV may be a treatment option for dogs experiencing restenosis after BPV or those in which restenosis is considered likely. Further study to evaluate the efficacy and safety of this approach is needed.

Atenolol in cats with subclinical hypertrophic cardiomyopathy: a double-blind, placebo-controlled, randomized clinical trial of effect on quality of life, activity, and cardiac biomarkers.

OBJECTIVE: To compare quality of life (QOL) and activity measures between healthy control cats and cats with subclinical hypertrophic cardiomyopathy (HCM), and to evaluate the effect of oral atenolol therapy on QOL, activity, and circulating biomarkers in cats with subclinical HCM. ANIMALS: Thirty-two client-owned cats with subclinical HCM and 27 healthy control cats. METHODS: Owner responses to a QOL questionnaire, circulating cardiac biomarker concentrations, and accelerometer-based activity measures were compared prospectively in cats with and without HCM, and in cats with HCM before and after treatment with oral atenolol (6.25 mg/cat q 12 h) for 6 months. RESULTS: Owner-assessed activity of daily living score was lower in cats with HCM than in cats in controls (p=0.0420). No differences were identified between control cats and cats with HCM for any activity variable. Compared with placebo, treatment with atenolol was associated with a lower baseline-adjusted mean ± SD heart rate (157 ± 30 vs. 195 ± 20 bpm; p=0.0001) and rate-pressure product (22,446 ± 6,237 vs. 26,615 ± 4,623 mmHg/min; p=0.0146). A treatment effect of atenolol on QOL or activity was not demonstrated. CONCLUSIONS: This study failed to identify an effect of subclinical HCM on owner-assessed QOL or activity or a treatment effect of atenolol on these variables at the dosage evaluated. These findings do not support a treatment benefit of atenolol for the goal of symptom reduction in cats with subclinical HCM.

Preliminary investigation of orally administered benazepril in horses with left-sided valvular regurgitation.

BACKGROUND: Despite the paucity of data available, orally administered angiotensin-converting enzyme (ACE) inhibitors are empirically used in horses with valvular regurgitation. OBJECTIVE: Evaluate the echocardiographic and hormonal changes in response to oral benazepril in horses with left-sided valvular regurgitation. STUDY DESIGN: Prospective, randomised double-blind, placebo-controlled trial. METHODS: Horses with mitral valve (MR) and/or aortic valve regurgitation (AR) received oral benazepril (n = 6) at a dosage of 1 mg/kg q 12 h or a placebo (n = 5) for 28 days. Echocardiography was performed before drug administration and after 28 days of treatment. Plasma renin activity, serum ACE activity, angiotensin II concentration, aldosterone concentration and biochemical variables were measured before drug administration and after 7 and 28 days of treatment. RESULTS: Relative to baseline, horses treated with benazepril had statistically significant reduction in left ventricular internal diameter in systole (mean difference between groups = -0.97 cm; 95% CI = -1.5 to -0.43 cm), aortic sinus diameter (-0.31 cm; -0.54 to -0.07 cm), and percentage of the aortic annulus diameter occupied by the base of the AR jet (-17.05%; -31.17 to -2.93%) compared with horses receiving a placebo. In addition, horses treated with benazepril had a significantly greater increase in cardiac output (11.95 L/min; 1.17-22.73 L/min) and fractional shortening (7.59%; 3.3-11.88%) compared with horses receiving a placebo. Despite profound serum ACE inhibition, renin activity and concentrations of angiotensin II and aldosterone were not significantly different between treatment groups or among time points. MAIN LIMITATIONS: Very small sample size and short treatment period. CONCLUSIONS: Treatment with oral benazepril resulted in statistically significant echocardiographic changes that might indicate reduced cardiac afterload in horses with left-sided valvular regurgitation. Additional studies with a larger sample size will be necessary to determine if administration of benazepril is beneficial in horses with valvular regurgitation. The Summary is available in Spanish - see Supporting Information.

A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)-to-M transition.

We describe a novel nuclear factor called mitotic chromosome-associated protein (MCAP), which belongs to the poorly understood BET subgroup of the bromodomain superfamily. Expression of the 200-kDa MCAP was linked to cell division, as it was induced by growth stimulation and repressed by growth inhibition. The most notable feature of MCAP was its association with chromosomes during mitosis, observed at a time when the majority of nuclear regulatory factors were released into the cytoplasm, coinciding with global cessation of transcription. Indicative of its predominant interaction with euchromatin, MCAP localized on mitotic chromosomes with exquisite specificity: (i) MCAP-chromosome association became evident subsequent to the initiation of histone H3 phosphorylation and early chromosomal condensation; and (ii) MCAP was absent from centromeres, the sites of heterochromatin. Supporting a role for MCAP in G(2)/M transition, microinjection of anti-MCAP antibody into HeLa cell nuclei completely inhibited the entry into mitosis, without abrogating the ongoing DNA replication. These results suggest that MCAP plays a role in a process governing chromosomal dynamics during mitosis.

Attenuation of the blood pressure response to exogenous angiotensin I after oral administration of benazepril to healthy adult horses.

BACKGROUND: Benazepril has been shown to inhibit circulating angiotensin-converting enzyme (ACE) activity in horses but the optimal dosage is unknown. OBJECTIVES: To determine the lowest tested dose of benazepril that results in ≥75% attenuation in the response of arterial blood pressure (BP) to exogenous angiotensin I (ANG-I) administration. STUDY DESIGN: Prospective experimental study. METHODS: A total of 5 healthy horses were instrumented for the direct measurement of BP. Each horse received 4 intragastric doses of benazepril (0.5, 1, 2 and 4 mg/kg bwt) with a washout period of 7 days between doses. Prior to and 2, 12 and 24 h after benazepril administration, each horse received intravenous (i.v.) boluses of ANG-I at 20, 60 and 200 ng/kg. Attenuation of the systolic arterial pressure (SBP) response to ANG-I and serum ACE activity were quantified and expressed as percentage of inhibition. RESULTS: There was a significant effect of benazepril dose (P = 0.004) and time (P = 0.004) on the percentage of inhibition of the systolic pressor response to ANG-I. Regardless of benazepril dose, the percentage of inhibition was significantly greater 2 h after administration of benazepril compared with 12 and 24 h. At an ANG-I dose of 20 ng/kg, the percentage of inhibition after administration of benazepril at 1 mg/kg bwt (46.6 ± 18.9%) was significantly greater than that achieved after 0.5 mg/kg bwt (19 ± 14%) but not significantly different from that achieved at higher doses of benazepril. Benazepril doses ≥1 mg/kg bwt resulted in serum ACE inhibition of at least 90%. MAIN LIMITATIONS: Small sample size and resulting low statistical power. CONCLUSIONS: Attenuation of the rise in SBP in response to ANG-I after administration of benazepril is modest in horses despite adequate serum ACE inhibition. A dose of 1 mg/kg bwt would be recommended for future investigations of benazepril for the management of cardiovascular diseases in horses.

Previously hidden chromosome aberrations in T(12;15)-positive BALB/c plasmacytomas uncovered by multicolor spectral karyotyping.

The majority of BALB/c mouse plasmacytomas harbor a balanced T(12;15) chromosomal translocation deregulating the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, the possible contribution of additional chromosomal aberrations to the progression of plasmacytoma development has been largely ignored. Here we use multicolor spectral karyotyping (SKY) to evaluate 10 established BALB/c plasmacytomas in which the T(12;15) had been previously detected by G banding. SKY readily confirmed the presence of this translocation in all of these tumors and in three plasmacytomas newly identified secondary cytogenetic changes of the c-myc-deregulating chromosome (Chr) T(12;15). In addition, numerous previously unknown aberrations were found to be scattered throughout the genome, which was interpreted to reflect the general genomic instability of plasmacytomas. Instability of this sort was not uniform, however, because only half of the tumors were heavily rearranged. Seven apparent hot spots of chromosomal rearrangements (40% incidence) were identified and mapped to Chrs 1B, 1G-H, 2G-H1, 4C7-D2, 12D, 14C-D2, and XE-F1. Two of these regions, Chr 1B and Chr 4C7-D2, are suspected to harbor plasmacytoma susceptibility loci; Pctr1 and Pctr2 on Chr 4C7-D2 and as yet unnamed loci on Chr 1B. These results suggest that secondary chromosomal rearrangements contribute to plasmacytoma progression in BALB/c mice. To evaluate the biological significance of these rearrangements, SKY will be used in follow-up experiments to search for the presence of recurrent and/or consistent secondary cytogenetic aberrations in primary BALB/c plasmacytomas.

Cardiovascular effects of pimobendan in healthy mature horses.

REASONS FOR PERFORMING STUDY: Pimobendan is an inodilator used in dogs for the management of heart failure due to myxomatous valve disease or dilated cardiomyopathy. The lack of data regarding the effects of pimobendan in horses prevents the rational use of this drug. OBJECTIVE: To determine the cardiovascular effects of pimobendan in healthy mature horses. STUDY DESIGN: Randomised experimental study. METHODS: Five horses were fasted overnight prior to receiving i.v. pimobendan (0.25 mg/kg bwt), intragastric (i.g.) pimobendan (0.25 mg/kg bwt) or i.g. placebo with a washout period of one week between each administration. Horses were instrumented for the measurement of right ventricular (RV) minimum pressure, RV maximum pressure, RV end diastolic pressure, and maximum rate of increase and decrease in RV pressure before and 0.5, 1, 2, 4, and 8 h after drug administration. Arterial blood pressure, central venous pressure, cardiac output and heart rate were measured at the same time points. Data were expressed as a maximum percentage of change over baseline values. RESULTS: There were no adverse effects associated with administration of pimobendan. The percentage increase in heart rate was significantly greater for horses given pimobendan i.g. (33 ± 4%) and i.v. (36 ± 14%) than for those given a placebo (-2 ± 7%). The percentage increase in maximum rate of increase in RV pressure (35 ± 36%) and the percentage decrease in minimum pressure (47 ± 24%) and end diastolic pressure (34 ± 13%) were significantly greater in horses given pimobendan i.v. than in those given placebo. Other variables measured were not significantly different between treatment groups. CONCLUSION: Pimobendan administered i.v. has positive chronotropic and inotropic effects in healthy mature horses and warrants further investigation for the treatment of heart failure in horses.

Congestive heart failure caused by transvenous pacemaker lead prolapse and associated right ventricular outflow tract obstruction in a dog.

A 16-year-old dog was presented for cough as well as increased respiratory rate and effort three years after implantation of a single-lead transvenous artificial pacemaker system. Thoracic radiographs and echocardiography disclosed prolapse of the pacemaker lead into the main pulmonary artery, causing severe pulmonary insufficiency and right-sided volume overload. Repositioning of the pacemaker lead led to improvement of pulmonary insufficiency and resolution of the dog's clinical signs and cavitary effusions. This case describes a late complication of pacemaker implantation that may be avoided by appropriate use of the manufacturer-provided anchoring sleeve and avoidance of excessive lead redundancy.

Recurrent non-reciprocal translocations of chromosome 5 in primary T(12;15)-positive BALB/c plasmacytomas.

The majority of inflammation-induced peritoneal BALB/c plasmacytomas (approximately 90%) harbor a balanced T(12;15) chromosomal translocation that deregulates the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, plasmacytomas take a long time to develop (average tumor latency approximately 220 days), which suggests that additional tumor progression events may be required to complete oncogenesis. We hypothesized that such tumor progression events may take the form of secondary chromosomal aberrations that can be detected by spectral karyotyping (SKY). We screened the entire chromosome complement of 18 primary BALB/c plasmacytomas carrying the T(12;15) and found in nine tumors (50% recurrence) secondary cytogenetic aberrations that involved bands D, E and F chromosome (Chr) 5. The Chr 5D-F rearrangements were manifested predominantly as unbalanced translocations with various partner chromosomes. This finding led us to propose the existence of an important plasmacytoma progression locus in the central region of Chr 5, which presumably becomes involved in peritoneal plasmacytoma development by promiscuous chromosomal translocations.

Cytogenetic analysis of the bipotential murine pre-B cell lymphoma, P388, and its derivative macrophage-like tumor, P388D1, using SKY and CGH.

Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) were used to elucidate the divergent cytogenetic make-up of the prototypical bilineage lymphoblastic pre-B lymphoma, P388, and its progenitor macrophage-like tumor, P388D1. P388 was found to be diploid and genomically stable. P388D1 was triploid, highly unstable and characterized by numerous marker chromosomes (Chrs) and composite rearrangements. The karyotype of P388D1 was so complex that its clonal relatedness to P388 would have remained questionable without confirmation by molecular analysis of the clonotypic immunoglobulin heavy-chain and light-chain gene recombinations that coexisted in both tumors. The intrinsic instability of the P388D1 genome was indicated by the observation that only four out of 42 aberrations uncovered by SKY (in a total of 27 metaphases) occurred consistently (100% incidence), whereas 27 changes occurred non-randomly (27 to 96% incidence) and 11 alterations randomly (4 to 11% incidence). Persistent cytogenetic instability was also observed in P388 'macrophages' after phorbol ester- and ionomycin-induced conversion in vitro of P388 lymphoma cells. The 'cytogenetic noise' in these cells was manifested by a multiplicity of sporadic chromosomal aberrations; ie 25 distinct changes were identified by SKY in 40 metaphases. The results in P388D1 and P388 'macrophages' were interpreted to indicate that the myeloid differentiation program in the bipotential pre-B cell lymphoma P388 is invariably characterized by karyotypic instability. The study presented here demonstrates the power of the combined SKY and CGH approach to resolve complicated karyotypes of important and widely used mouse tumors.

Effect of oral mineral and energy supplementation on blood mineral concentrations, energetic and inflammatory profile, and milk yield in dairy cows affected with dystocia.

The objectives of this study were to determine the effect of mineral/energy supplementation of dairy cows with dystocia on blood mineral concentrations, energetic and inflammatory profiles, and milk yield. Multiparous Holstein cows with dystocia were randomly assigned into two groups, (1) treated with a mineral/energy supplement (DME, n= 18) and (2) not treated (DNT, n= 22). A group of cows with normal parturition were randomly selected and were left untreated (NNT, n= 25). Cows in DME received an oral drench of 110 g of calcium and 400 g of propionate as calcium propionate plus 110 g potassium chloride and 150 g of magnesium sulfate administered within 6 h of calving and again 3 days post-partum. Compared to cows with a normal parturition, dystocic cows had decreased plasma calcium concentrations, increased plasma haptoglobin, decreased milk yield at 1 day post-partum, and tended to have increased rectal temperatures from 1 to 12 days post-partum. Compared with cows in DNT, those in DME had decreased plasma calcium concentrations and increased plasma magnesium concentrations 2 and 3 days post-partum, and a tendency for an increase in rectal temperature from 1 to 12 days post-partum. Dystocia is detrimental to calcium homeostasis post-partum, but mineral/energy supplementation as undertaken in this study is not recommended for use in cows with dystocia.

Late-onset congenital adrenal hyperplasia: a treatable cause of anxiety.

BACKGROUND: Some intermediaries of cortisol synthesis, especially the sulfated ester of dehydroepiandrosterone (DHEAS), are picrotoxin-like antagonists of the gamma-aminobutyric acid A (GABA-A) receptor and exert potent anxiogenic effects. We report 5 men and 7 women with refractory anxiety disorders, who had late-onset congenital adrenal hyperplasia (CAH), and in whom interactions between neuroactive steroids and anomalous brain substrates may have participated in the pathophysiology and treatment of anxiety. METHODS: Twelve patients with refractory anxiety disorders as defined by DSM-IV had elevated DHEAS and specific enzyme deficiencies diagnostic of CAH. All were treated with adrenal suppressive therapy using ketoconazole or low (physiologic) dose glucocorticoids. Anxiety was rated by the Tension Scale of the Profile of Mood States (POMS Tension) questionnaire before and during hormonal treatment. RESULTS: Reduction of DHEAS was associated with lower anxiety scores in all twelve cases. POMS Tension scores decreased by 55%. Hormonal treatment, which failed to lower DHEAS, was ineffective. CONCLUSIONS: These findings suggest that late onset CAH can contribute to anxiety disorders and that adrenal suppressive therapy or inhibition of steroidogenesis with ketoconazole may be efficacious as adjuvant therapy.

Altered pulsatile secretion of luteinizing hormone in women with epilepsy.

Menstrual disorders and infertility are common among women with epilepsy of temporal lobe origin (TLE). Reproductive endocrine disorders may be the cause. Polycystic ovarian syndrome (PCO) and hypothalamic amenorrhea (hypogonadotropic hypogonadism, HH), in particular, are significantly overrepresented and attributable to hypothalamic dysfunction. We therefore compared the hypothalamic function of 14 women with clinically and electrographically documented TLE with that of eight age-matched normal controls by determining the interictal pulse frequency and amplitude of luteinizing hormone (LH) secretion. Serum for LH measurement was drawn every 15 minutes from 8 AM to 4 PM in both groups. LH pulse frequency values were significantly more variable (p < 0.05) and lower (p < 0.05) among women with TLE than among controls. Women with left temporal EEG foci showed a trend toward higher pulse frequencies compared to women with right foci (p = 0.05 to 0.10). Among five women with reproductive endocrine disorders, the three with PCO had left-sided foci and average LH pulse frequency two times higher than that of the two women with HH, who had right-sided foci. Eight reproductively normal, medically treated women with TLE had significantly lower LH pulse frequencies than did the one reproductively normal, untreated woman with TLE (p < 0.05) and the eight normal controls (p < 0.001). These findings suggest that LH pulse frequencies in women with TLE may be influenced by the laterality of the epileptic focus, the reproductive endocrine status, and the use of antiseizure medications.

Genomic organisation and expression of BCL6 in murine B-cell lymphomas.

BCL6 encodes a transcription factor deregulated by chromosomal translocations in human diffuse large cell B lymphomas (DLCL). This study was designed to determine whether Bcl6 might also be involved in lymphomas of mice. BCL6 protein was expressed at high levels in 90% or more of DLCL but not in low grade B lymphomas. Southern hybridisation studies demonstrated altered organisation of Bcl6 in three primary DLCL and the WEHI 231 B-cell lymphoma cell line but not in low grade tumours. Chromosomal painting and fluorescence in situ hybridisation (FISH) analyses of the WEHI 231 metaphase spreads revealed a T(5;16) translocation with Bcl6 on Chromosome 16 at the translocation breakpoint. Deregulated expression of BCL6 is thus likely to contribute to the genesis of DLCL of mice as well as of humans.

Conformational differences in the 3-D nanostructure of the immunoglobulin heavy-chain locus, a hotspot of chromosomal translocations in B lymphocytes.

Spectral precision distance microscopy was utilized to detect small but nonetheless consistently present conformational differences between the immunoglobulin heavy-chain gene clusters (IgH) that reside on the two chromosome 12 homologues in all diploid cells of the mouse. The euclidian distance (i.e., the mean arithmetic three-dimensional [3-D] distance) between the 5' most IgH gene, C mu, and the 3' most IgH gene, C alpha, was used as the indicator to define the co-presence of a condensed IgH domain and a relaxed IgH domain in the same cell. In normal and malignant B cells in which IgH is actively rearranged and transcribed, the C mu/C alpha distance (genomic distance approximately 180 kb) was found to range from 87.5 to 121 nm on the condensed IgH domain and from 154 to 207 nm on the relaxed IgH domain. In non-B cells (fibroblasts, neutrophils, and macrophages), in which IgH is inactive, the C mu/C alpha distance was found to range from 136 to 154 nm on the condensed IgH domain and from 250 to 292 nm on the related IgH domain. These results suggested that conformational differences that may predispose the relaxed IgH domain for illegitimate genetic recombinations, such as chromosomal translocations, are likely to exist in many cell types, including B cells. However, in B lymphocytes this structural predisposition may conspire with the lineage-specific ability to activate proto-oncogenes (after juxtaposition to IgH) to positively affect the preferential involvement of the relaxed IgH domain in chromosomal translocations. Additional studies are warranted to validate this working hypothesis.

Differential laminar distribution of acetylcholinesterase and butyrylcholinesterase containing tangles in the cerebral cortex of Alzheimer's disease.

A sensitive histochemical method for the visualization of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was used to determine the laminar distribution of cholinesterase-positive cortical tangles in Alzheimer's disease (AD). In many cortical areas AChE- and BChE-positive tangles displayed a completely overlapping distribution. In other areas the most superficial layers contained only AChE-positive tangles whereas the deepest layers contained only BChE-positive tangles. These observations suggest that some cholinesterase-positive tangles have a predominantly (if not exclusively) AChE-like reactivity whereas others have a reactivity that is predominantly BChE-like. The intermingling of AChE- and BChE-positive tangles in most cortical areas and layers suggests that there may also be a third population in which the two enzymes are equally prominent in the same tangle.