Monophasic action potential recordings during acute changes in ventricular loading induced by the Valsalva manoeuvre.

OBJECTIVE--The strong association between ventricular arrhythmia and ventricular dysfunction is unexplained. This study was designed to investigate a mechanism by which a change in ventricular loading could alter the time course of repolarisation and hence refractoriness. A possible mechanism may be a direct effect of an altered pattern of contraction on ventricular repolarisation and hence refractoriness. This relation has been termed contraction-excitation feedback or mechano-electric feedback. METHODS--Monophasic action potentials were recorded from the left ventricular endocardium as a measure of the time course of local repolarisation. The Valsalva manoeuvre was used to change ventricular loading by increasing the intrathoracic pressure and impeding venous return, and hence reducing ventricular pressure and volume (ventricular unloading). PATIENTS--23 patients undergoing routine cardiac catheterisation procedures: seven with no angiographic evidence of abnormal wall motion or history of myocardial infarction (normal), five with a history of myocardial infarction but with normal wall motion, and 10 with angiographic evidence of abnormal wall motion--with or without previous infarction. One patient was a transplant recipient and was analysed separately. SETTING--Tertiary referral centre for cardiology. RESULTS--In patients with normal ventricles during the unloading phase of the Valsalva manoeuvre (mean (SD)) monophasic action potential duration shortened from 311 (47) ms to 295 (47) ms (p less than 0.001). After release of the forced expiration as venous return was restored the monophasic action potential duration lengthened from 285 (44) ms to 304 (44) ms (p less than 0.0001). In the group with evidence of abnormal wall motion the direction of change of action potential duration during the strain phase was normal in 7/21 observations, abnormal in 6/21, and showed no clear change in 8/21. During the release phase 11/20 observations were normal, five abnormal, and four showed no clear change. In those with myocardial infarction four out of five patients had changes that resembled those with normal ventricles but the changes were less pronounced. There were no differences in any of the three groups between the changes in monophasic action potential duration in patients taking beta blockers and those who were not. The changes in monophasic action potential duration in the transplanted heart resembled those in the group with normal ventricles. Inflections on the repolarisation phase of the monophasic action potential consistent with early afterdepolarisations were seen in three of the patients with abnormal wall motion and in none of those with normal wall motion. CONCLUSIONS--These results are further evidence that changes in ventricular loading influence repolarisation. When wall motion was abnormal the effects on regional endocardial repolarisation were often opposite in direction to those when it was normal. Thus regional differences in wall motion could generate local electrophysiological inhomogeneity which may be relevant to the association of arrhythmia with impaired left ventricular function.     

Cardiovascular adaptations to transfusion/chelation therapy of homozygote sickle cell anemia

The effect of transfusion/chelation therapy on the cardiovascular adaptations to chronic anemia in pediatric and young adult patients with homozygous sickle cell disease is uncertain. This study compares left ventricular (LV) function indexes and thoracoabdominal aortic systolic and diastolic blood flow in nontransfused and transfused patients with homozygous sickle cell disease. The study population consisted of 29 nontransfused patients with homozygous sickle cell disease, ages 0.4 to 20.9 years (group 1) and 11 chronically transfused/chelated patients, ages 4.0 to 21.8 years (group 2). The mean total hemoglobin concentration in group 2 was 28% greater than that in group 1. The mean duration of transfusion/chelation therapy in group 2 was 3.7 years. The percent of predicted LV end-diastolic and end-systolic dimensions were significantly greater than the respective controls in both groups. There was no significant difference in percent of predicted LV end-diastolic dimension (group 1, 120 +/- 12%; group 2, 120 +/- 12%) or percent of predicted LV end-systolic dimension (group 1, 120 +/- 12%; group 2, 117 +/- 8) between the groups. The percent of LV shortening fraction was similar in study groups and control subjects. Aortic systolic blood flow (cc/min/m2) for group 1 (2,426 +/- 841) and 2 (2,374 +/- 1.004) were significantly greater than corresponding control values (1,683 +/- 442, 1,736 +/- 430, respectively). Aortic diastolic blood flow was significantly greater than corresponding control values for both group 1 (699 +/- 313 vs 488 +/- 212) and group 2 (1,080 +/- 607 vs 588 +/- 219).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reformulation and drop size of apraclonidine hydrochloride.

We performed a prospective, double-masked, placebo-controlled, six-period, cross-over study in which normal subjects were randomly assigned to treatment and compared three different formulations of apraclonidine hydrochloride (the present commercially available formulation, and formulations with hydroxypropylmethylcellulose or lysolecithin). We also evaluated the efficacy of a 16-microliters and 30-microliters drop size. The magnitude and duration of decrease in intraocular pressure was comparable for all formulations. Most subjects tolerated all formulations well with only a few reporting any side effects. The best-tolerated formulation was 0.5% apraclonidine hydrochloride delivered with a 16-microliters drop size. Dry mouth developed frequently with the commercially available 1% apraclonidine solution. Blurred vision complicated the use of the formulation containing hydroxypropylmethylcellulose. Both dry mouth (P less than .05) and blurred vision (P = .004) were statistically significant side effects.     

Flow cytometric DNA analysis of placental-site trophoblastic tumors.

The placental-site trophoblastic tumor is a rare form of gestational trophoblastic neoplasia. Although originally considered benign, it is now apparent that this lesion can be associated with aggressive clinical behavior. Our study examined the DNA ploidy status and clinicopathologic features of four new cases of placental-site trophoblastic tumor. Three cases demonstrated diploid DNA stemlines with S-phase fractions ranging from 6% to 16%. These patients were alive and well at follow-up and had low-serum human chorionic gonadotrophin (hCG) levels. A fourth patient, who had a large tumor, demonstrated a tetraploid DNA peak with a prominent S-phase fraction. This patient exhibited an elevated serum hCG at limited follow-up. Flow cytometric DNA analysis may be a useful adjunct for the identification of placental-site trophoblastic tumors with malignant potential.     

D-cycloserine augmented exposure therapy for obsessive-compulsive disorder.

BACKGROUND: D-cycloserine (DCS), a glutamatergic partial N-methyl-d-aspartate (NMDA) agonist, can facilitate extinction learning related to cued fear in animals and humans. We predicted that DCS would accelerate obsession-related distress reduction in patients with obsessive-compulsive disorder (OCD) undergoing extinction-based exposure therapy. METHODS: We administered DCS (125 mg) or placebo in a double-blind fashion to individuals with OCD approximately 2 hours before each exposure session. RESULTS: D-cycloserine decreased both the number of exposure sessions required to achieve clinical milestones and the rate of therapy dropout. After four exposure sessions, patients in the DCS group reported significantly greater decreases in obsession-related distress compared with the placebo group; however, after additional sessions, the placebo group tended to catch up. CONCLUSIONS: D-cycloserine augmentation has the potential to increase the efficiency, palatability, and overall effectiveness of standard exposure therapy for OCD.     

An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain.

In search of genes possibly involved in the regulation of hindbrain segmentation, we have isolated mouse cDNA clones corresponding to putative protein kinase genes by polymerase chain reaction amplification of cDNA from 9.5-day-old embryo hindbrains. In situ hybridization analysis revealed that one of these genes, Sek, was expressed in an alternating segment-restricted pattern in the developing hindbrain. Isolation and analysis of Sek cDNAs covering the entire coding sequence indicated that Sek encoded a putative receptor protein tyrosine kinase, belonging to the Eph family. These data are consistent with a role of the Sek gene product in a signal transduction process involved in pattern formation in the hindbrain.     

Allodynia in rats infected with varicella zoster virus—a small animal model for post-herpetic neuralgia

The most common complication of herpes zoster is post-herpetic neuralgia (PHN), which has been defined as severe pain occurring 1 month after rash onset or persisting for greater than 3 months. PHN is classed as a neuropathic pain that is associated with mechanical allodynia where normally innocuous tactile stimuli are perceived as painful. The development of therapies to treat PHN has been hampered by the lack of animal models, which mimic the clinical situation. We have previously reported that varicella zoster virus (VZV) infection in the rat results in mechanical allodynia and thermal hyperalgesia. Here, we report that following VZV infection of the left footpad rats develop a chronic mechanical allodynia, which is present for longer than 60 days post-infection and which resolves by 100 days PI. The model is robust and reproducible with animals consistently developing allodynia by 3 days PI and continuing to present with symptoms for at least 30 days. The reproducible nature of the induction and course of the allodynia allows the use of this model to determine the effect of various compounds on, and to investigate the pathogenic mechanisms underlying the development of VZV-induced allodynia. Comparative studies using HSV-1 show that the induction of the chronic allodynia is VZV-specific and is not a result is of virus replication-induced tissue damage or accompanying inflammation.Therefore, we propose that the rat VZV infection model could prove useful in studying the mechanisms underlying post-herpetic neuralgia.     

Initial experience with carbon dioxide laser laparoscopy

Adhesions and endometriosis are commonly encountered among patients presenting with pelvic or lower abdominal pain and also in a significant proportion of infertile patients. Laparoscopic investigation is usual in patients with these problems, and it has been possible to perform endoscopic surgery with special scissors and electrodiathermy. These methods can cause troublesome bleeding, and the diathermy produces high temperatures which can be hazardous if used in the vicinity of the bowel. The carbon dioxide laser can be used endoscopically to vaporize deposits of endometriosis and adhesions with great precision and virtually no bleeding. One hundred consecutive patients with endometriosis or adhesions were treated with the CO₂ laser laparoscope and followed up for at least a year. Seventy-five per cent of patients with pain due to endometriosis were cured, and 68% of patients were better after laser laparoscopic adhesiolysis. Pregnancy rate in the previously infertile group with endometriosis was 64%. There were no complications due to the intra-abdominal use of CO₂ laser energy under endoscopic control, although there is a need for a controlled trial. It appears that in the hands of an experienced laparoscopist this technique is safe and effective.