Patient satisfaction and symptom relief after anal dilatation

Anal dilatation is used as a simple method of treatment and has been used for both anal fissure and haemorrhoids. This study examined longer-term results among a cohort of 162 patients, 132 of whom responded to a detailed questionnaire, an 82% response (66 patients were male; age range 17-75 years, median 42 years). Follow-up ranged from 16 months to 36 months (median 27 months) after anal dilatation (68 patients for fissure, 32 for haemorrhoids, and 32 for both). In the early months after dilatation, 83% had symptomatic improvement and 76% remained improved. Five (7%) patients with fissure and 11 with haemorrhoids (17%) required further hospital treatment, while 10% and 17%, respectively, had received further treatment from their general practitioners (GPs). Seventy-one percent said they would have a further anal dilation if symptoms recurred. There was no difference in results obtained by surgeons of different seniority. Complications--bleeding (29%) and difficulty controlling flatus (15%) or faeces (8%)--resolved in all cases. The results of anal dilatation for fissure are generally satisfactory in the longer term, with a trend toward better symptom relief in patients with fissure compared with those with haemorrhoids. We do not recommend anal dilatation as the sole treatment of patients with haemorrhoids, but it may be a useful adjunct to other treatments such as banding or sclerotherapy. Morbidity was generally acceptable and the majority of our patients would be prepared to have this procedure again if their symptoms were to return.     

Reduced MTR in the corticospinal tract and normal T2 in amyotrophic lateral sclerosis

The objective of this study was to test the hypothesis that magnetization transfer ratios (MTR) are decreased in the corticospinal tract of patients with amyotrophic lateral sclerosis (ALS); to determine if T2 is increased in corticospinal tract or reduced in motor cortex in ALS; to determine if corticospinal tract MTR correlates with a clinical measure of motor neuron function in ALS. Ten ALS patients and 17 age-matched controls were studied. Double spin echo MRI and 3D gradient echo MRI with and without off-resonance saturation were acquired on each subject. 3D data sets were coregistered and resliced to match the spin echo data set. MTR was calculated for corticospinal and non-corticospinal tract white matter. T2 was calculated for corticospinal and non-corticospinal tract white matter, motor cortex and non-motor cortex. MTR was reduced by 2.6% (p < .02) in corticospinal, but not in non-corticospinal, tract white matter in ALS. There was no difference in T2 in any brain region. The correlation between a clinical measure of motor neuron function and corticospinal tract MTR was statistically significant. These findings are consistent with the known pathology in ALS and suggest that MTR is more sensitive than T2 for detecting involvement of the corticospinal tract. Quantitative MTR of the corticospinal tract may be a useful, objective marker of upper motor neuron pathology in ALS.     

Endoscopic malar/midface suspension procedure

Aging in the midface area is seen with ptosis of the malar tissues, hollowing of the infraorbital area, deepening of the nasolabial and mandibular labial folds, and increased jowling. Some of these aging changes are usually not corrected by a standard SMAS face lift. An endoscope-dependent technique was created specifically to address the midface area. The midface tissues are elevated and released in a subperiosteal manner and then suspended to a higher position after endoscopic dissection of the temporal area. The tissues are repositioned to a higher position on the malar area with softening of the nasolabial fold, decreased jowls, and recreation of the desired youthful fullness in the malar and infraorbital area. This procedure can be combined easily with other facial procedures such as rhytidectomy, neck lift, temple lift, and laser resurfacing when indicated. More than 200 procedures have been completed in the last 22 months. This report presents the surgical technique with early follow-up results.     

Longitudinal examination of American National Adult Reading Test (AMNART) performance in dementia of the Alzheimer type (DAT): validation and correction based on degree of cognitive decline

The American National Adult Reading Test (AMNART) was constructed to provide a valid and stable estimate of premorbid verbal IQ (VIQ) in dementing individuals. However, recent studies have brought into question its validity in patients with dementia of the Alzheimer type (DAT). The present study was designed to longitudinally assess the validity of the AMNART in 40 DAT patients and 40 demographically matched normal control (NC) subjects. The results showed that VIQ estimates for patients with DAT were significantly lower than those of NC subjects and declined significantly over time with increasing dementia severity as measured by the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). An MMSE-based correction factor was derived for the DAT group which allows for the effective estimation of premorbid VIQ in these patients.     

Developmental and environmental factors that enhance binding of Bordetella pertussis to human epithelial cells in relation to sudden infant death syndrome (SIDS)

The pharmacokinetic properties of glucagon-like peptide-1(7-36)amide (GLP-1(7-37) were compared. Four beagle dogs received on 4 separate occasions s.c. bolus doses of 50 micrograms/kg, and 2 min i.v. infusions of 50 micrograms/kg of each peptide. The plasma immunoreactivity of GLP-1 (P-GLP-1-IR) was measured by a sandwich enzyme-linked immunosorbent assay (ELISA). After i.v. infusion, the plasma half-life in the first-phase was 2.1 +/- 0.1 and 2.4 +/- 0.3 min, in the final-phase 68 +/- 6 and 81 +/- 3 min, the total plasma clearance 25 +/- 3 and 22 +/- 4 ml/kg.min, the volume of distribution at steady state 0.16 +/- 0.02 and 0.84 +/- 0.24 l/kg, and the mean residence time 6.2 +/- 0.3 and 36 +/- 5 min for GLP-1(7-36)amide and GLP-1(7-37), respectively. After s.c. administration, the maximum plasma concentration was reached after 15 +/- 5 and 19 +/- 4 min and the absolute bioavailability was 48 +/- 7 and 49 +/- 13% for GLP-1(7-36)amide and GLP-1(7-37), respectively. P-GLP-1-IR, measured by a radioimmunoassay (RIA), was considerably higher than when measured by ELISA. This discrepancy was due to cross-reactivity with metabolites of the parent peptide. The plasma degradation was studied in vitro in dog plasma at 37 degrees C, and the half-lives were found to be 61 +/- 9 and 132 +/- 16 min for GLP-1(7-36)amide and GLP-1(7-37), respectively (n = 6). Bacitracin inhibited the degradation of both peptides.     

Genetic control of anti-idiotypic vaccination against coronavirus infection

The idiotypic network can be experimentally altered to induce protective immune responses against microbial pathogens. Both internal image and noninternal image anti-idiotypic (anti-Id) antibodies have been shown to trigger antigen (Ag)-specific immune responses. Therefore, mechanisms of anti-Id vaccination appear to go beyond structural mimicry of Ag, but remain undefined. Using the neurotropic murine coronavirus animal model, we have previously shown that a polyclonal noninternal image anti-Id (Ab2) could vaccinate BALB/c mice. To characterize its mode of action, we have examined the immune modulating capability of this Ab2 in vivo in strains of mice with different H-2 haplotypes. Even though only internal image anti-Id are expected to induce non-genetically restricted immunity, this noninternal image Ab2 induced protective immunity in four of eight genetically different strains of mice susceptible to coronavirus infection. These were BALB/c (H-2d), DBA/2 (H-2d), DBA/1 (H-2q), and SWR (H-2q) mice. Protection was generally correlated with the induction of specific antiviral Ab (Ab3) that showed biological properties, such as virus neutralization in vitro, similar to the initial Ab1. To evaluate the genetic implication of the H-2 haplotypes in protection, congenic mice were also tested. Vaccination profiles suggest that cooperation between background gene(s) of the BALB/c mouse with H-2d and H-2q loci is necessary for an optimal protective immune response, although the main genetic element(s) regulating the antiviral response to Ab2 inoculation appeared to be located outside the major histocompatibility complex. These results are consistent with the ability of Ab2 to induce protective antiviral antibodies in genetically different animals by biological mimicry.     

8-Alkylamino-substituted analogs of N6-cyclopentyladenosine are partial agonists for the cardiovascular adenosine A1 receptors in vivo

Partial adenosine A1 receptor agonists with reduced intrinsic activity at the cardiovascular system would be promising for therapeutic application (e.g., as antilipolytic agents). In the present study a series of 8-alkylamino [methyl (M)-, ethyl (E)-, propyl (P)-, butyl (B)- and cyclopentyl (CP)-] derivatives of N6-cyclopentyladenosine (CPA) were investigated in conscious normotensive rats. After intravenous administration of the compounds to rats, heart rate (HR) and mean arterial pressure were monitored continuously, and serial arterial blood samples were drawn for determination of the pharmacokinetics. The concentration-heart rate relationships of the compounds were described on the basis of an integrated pharmacokinetic-pharmacodynamic model. The blood concentration-time profiles of the compounds could be described best by a biexponential function. The derivatives of CPA had uniform pharmacokinetic properties. The larger volume of distribution at steady state of the 8-substituted analogs resulted in terminal half-lives (ranging from 17 to 24 min) which were significantly longer than for CPA (7 min). All derivatives of CPA produced less pronounced reductions in HR and MAP than CPA. The relationship between concentration and the reduction in HR was adequately described by the sigmoidal Emax model in individual rats given 8MCPA, 8ECPA and 8PCPA. 8BCPA and 8CPCPA were nearly inactive on heart rate. The in vivo EC50,u values for the reduction in HR (366 nM, 210 nM, 170 nM and 175 nM for 8MCPA, 8ECPA, 8PCPA and 8BCPA, respectively) were in the same order of magnitude as the affinities in receptor binding studies. The order of magnitude of the intrinsic activities (Emax) was CPA > 8MCPA > 8ECPA = 8PCPA > 8BCPA > 8CPCPA, which indicated partial agonism of the compounds in vivo. The in vivo parameter Emax correlated highly (r = 0.97) to the GTP shift observed in radioligand binding experiments.     

Regulation of phosducin phosphorylation in retinal rods by Ca2+/calmodulin-dependent adenylyl cyclase

The phosphoprotein phosducin (Pd) regulates many guanine nucleotide binding protein (G protein)-linked signaling pathways. In visual signal transduction, unphosphorylated Pd blocks the interaction of light-activated rhodopsin with its G protein (Gt) by binding to the beta gamma subunits of Gt and preventing their association with the Gt alpha subunit. When Pd is phosphorylated by cAMP-dependent protein kinase, it no longer inhibits Gt subunit interactions. Thus, factors that determine the phosphorylation state of Pd in rod outer segments are important in controlling the number of Gts available for activation by rhodopsin. The cyclic nucleotide dependencies of the rate of Pd phosphorylation by endogenous cAMP-dependent protein kinase suggest that cAMP, and not cGMP, controls Pd phosphorylation. The synthesis of cAMP by adenylyl cyclase in rod outer segment preparations was found to be dependent on Ca2+ and calmodulin. The Ca2+ dependence was within the physiological range of Ca2+ concentrations in rods (K1/2 = 230 +/- 9 nM) and was highly cooperative (n app = 3.6 +/- 0.5). Through its effect on adenylyl cyclase and cAMP-dependent protein kinase, physiologically high Ca2+ (1100 nM) was found to increase the rate of Pd phosphorylation 3-fold compared to the rate of phosphorylation at physiologically low Ca2+ (8 nM). No evidence for Pd phosphorylation by other (Ca2+)-dependent kinases was found. These results suggest that Ca2+ can regulate the light response at the level of Gt activation through its effect on the phosphorylation state of Pd.