Crystallographic characterization of geometry and conformation of TOAC,a nitroxide spin-labelled Cα,α-disubstituted glycine,in simple derivatives and model peptides *

The molecular and crystal structures of one derivative and two oligopeptides of TOAC, a nitroxide spin-labelled C^αα-disubstituted glycine, have been determined by X-ray diffraction. The derivative is the 5(4H)-oxazolone from Piv-TOAC-OH; the oligopeptides are Z-TOAC-(L-Ala)₂-NHtBu sesquihydrate and p BrBz-TOAC-(L-Ala)₂-TOAC-L-Ala-NHtBu hemihydrate. Incipient and fully developed right-handed 3₁₀-helical conformations are formed by both independent molecules in the asymmetric unit of the terminally blocked tripeptide amide and the terminally blocked pentapeptide amide, respectively. The average geometry and preferred conformation for the piperidine ring of the TOAC residues are also discussed in detail. © Munksgaard 1996.     

S-IgA CHOLERA TOXIN AND ROTAVIRUS ANTIBODY IN HUMAN COLOSTRUM

Abstract. S-IgA antibodies against cholera toxin and rotavirus were assayed in 43 colostral samples by means of an enzyme-linked immunosorbent assay (ELISA). All specimens contained specific S-IgA antibodies against both antigens. Significant antibody titres to the antigens were demonstrated in almost all colostral samples.     

AMOXICILLIN AND CLAVULANIC ACID IN THE TREATMENT OF ACTINOMYCETOMA

Background. Mycetoma is a relatively frequent disease in tropical countries. Drugs commonly used need a long period of treatment, and some cases are resistant to these drugs, especially those with bone or visceral involvement. The combination of amoxicillin-clavulanic acid has shown effectiveness against strains of Nocardia brasiliensis in vitro. Methods. We have used this combination in two cases of mycetoma caused by N. brasiliensis, both with bone involvement and resistance to the drugs usually used. A dose of three tablets a day for 5 to 6 months was given (each tablet contains 500 mg of amoxicillin and 125 mg of clavulanic acid). Results. Clinical and mycologic amelioration was observed in the two cases after completing the treatment. There were no side effects or relapses after 3 to 6 months of follow-up after treatment. Conclusions. We propose this antibiotic as a new option for the treatment of some special cases of actinomycetoma with bone or visceral involvement or resistance to the drugs commonly used in this disease.     

FUNCTIONAL ANATOMY OF CAVERNOUS HELICINE ARTERIOLES IN POTENT SUBJECTS

Purpose

We investigated the morphological and functional features of cavernous helicine arterioles in male potent subjects.

Materials and Methods

Ten young men reporting normal rigid erections which were confirmed by polysomnographic recording underwent power Doppler sonography of the cavernous helicine arterioles during flaccidity, after intracavernous injection of alprostadil, and after subsequent genital and audiovisual sexual stimulation.

Results

During flaccidity the helicine arterioles were never detected by power Doppler imaging while they became evident in all cases after alprostadil injection. They usually originated from the cavernous artery forming an acute angle and showed 3 orders of ramifications. Systolic and diastolic flow was present. After genital and audiovisual sexual stimulation, and achievement of maximum rigidity, the helicine arterioles were still evident but with only 1 or 2 orders of distal ramifications. Only systolic flow was present. During penile tumescence the helicine arterioles disappeared in all cases.

Conclusions

Using power Doppler sonography it is possible to investigate the functional anatomy of the cavernous helicine arterioles during the various phases of the erectile cycle. Our preliminary study suggests that the helicine arterioles are functionally inactive during penile flaccidity while they are activated during penile tumescence and continue to supply blood to the corpora also during maximum penile rigidity.     

PROSTATE SPECIFIC ANTIGEN VARIATION IN PATIENTS WITHOUT CLINICALLY EVIDENT PROSTATE CANCER

PURPOSE: We address long-term within individual variation of serum prostate specific antigen (PSA) in men without clinical or biopsy evidence of prostate cancer. MATERIALS AND METHODS: We studied 943 men from a prostate cancer screening program with 2 PSA (PSA1 and PSA2) measurements available. A third PSA (PSA3) was obtained from 571 men. Only participants with no clinical evidence of cancer were included in the study. Within individual PSA variability was calculated based on indexes of percent coefficient of variation, ratio difference and PSA velocity. The relationship among these indexes, interval between measurements and number of PSA samples was assessed. RESULTS: Mean interval was 670.4 days between PSA1 and PSA2, and 801.8 days between PSA2 and PSA3 (p<0.001). Mean coefficient of variation was 18% after 2 and 15.7% after 3 PSA measurements. Mean ratio differences were -0.047 ng./ml. for 2 and 0.033 ng./ml. for 3 samples. Mean PSA velocity was -0.128 ng./ml. per year for 2 and -0.055 ng./ml. per year for 3 samples, with 95% confidence intervals of 0.634 and 0.315, respectively. Variability was higher if only 2 PSA measurements were done (p<0.001). No clear relationship was found between individual variability and interval between measurements. CONCLUSIONS: PSA velocity is within normal limits in almost all men (more than 95%) without clinically relevant prostate cancer. PSA individual variability is not fully dependent on the time between measurements when intervals are long, and can be substantially decreased with a third PSA sample.     

Long-Term Outcomes of CRT-PM Versus CRT-D Recipients

Objective: To compare the rates of all-cause mortality in recipients of cardiac resynchronization therapy devices without (CRT-PM) versus with defibrillator (CRT-D).
Methods: Between February 1999 and July 2004, 233 patients (mean age = 69 ± 8 years, 180 men) underwent implantation of CRT-PM or CRT-D devices. New York Heart Association (NYHA) heart failure functional class II was present in 11%, class III in 69%, and class IV in 20% of patients; mean left ventricle ejection fraction (LVEF) was 26.5 ± 6.5 %, 48% presented with idiopathic dilated cardiomyopathy and 49% with ischemic heart disease. Cox multiple variable regression analysis was performed in search of predictors of death.
Results: The clinical characteristics of the 117 CRT-PM and 116 CRT-D recipients were similar, except for LVEF (28.2 ± 6.2% vs 25.0 ± 6.5%, respectively; P < 0.001), and ischemic versus nonischemic etiology of heart failure (41% vs 56%, respectively P = 0.02). Over a mean follow-up of 58 ± 15 months, no significance difference in overall mortality rate was observed between the two study groups. Male sex, NYHA functional class IV, and atrial fibrillation at implant were significant predictors of death.
Conclusions: There was no difference in long-term survival rate among patients with CRT-D versus CRT-PM, although CRT-D more effectively lowered the sudden death rate. Male sex, NYHA functional class IV, and atrial fibrillation predicted the worst prognosis.     

Clinical Utility of Intraatrial Pacemaker Stored Electrograms to Diagnose Atrial Fibrillation and Flutter

POLLAK, W.M., et al. : Clinical Utility of Intraatrial Pacemaker Stored Electrograms to Diagnose Atrial Fibrillation and Flutter. The purpose of this study was to determine if intraatrial electrograms (EGMs) are required to diagnose specific types of atrial tachyarrhythmias detected by pacemaker diagnostics. DDD pacemakers in 56 patients were programmed to store episodes of atrial tachyarrhythmias. Some episodes had a stored atrial EGM snapshot of the atrial tachyarrhythmia. The EGMs were analyzed to confirm whether the stored episodes were true atrial tachyarrhythmias or other pacemaker-sensed events. EGM confirmation of atrial tachyarrhythmias correlated with increasing duration and rate of episodes. In particular, using EGMs, 8 (18%) of 44 episodes < 10 seconds in duration confirmed atrial tachyarrhythmias compared to 16 (89%) of 18 episodes > 5 minutes in duration (  P < 0.001  ). Only 10 (18%) of 56 detected atrial arrhythmia episodes at rates < 250 complexes per minute were confirmed by the atrial EGM as true arrhythmias compared to 33 (57%) of 58 detected episodes at rates > 250/min (  P < 0.001  ) Twenty-nine (91%) of 32 EGM confirmed episodes of atrial fibrillation/flutter had an atrial rate > 250 complexes per minute and were a minimum of 10 seconds in duration. Fifteen (88%) of 17 episodes meeting the combined stored data criteria of > 250 complexes per minute and duration > 5 minutes were confirmed as atrial fibrillation or flutter by stored EGMs. Atrial EGMs identified that 71 (62%) of 114 stored high atrial rate (HAR) episodes were events other than true atrial tachyarrhythmias. Pacemaker diagnostic data with intraatrial EGMs can diagnose specific atrial tachyarrhythmias and identify other pacemaker-sensed events. Stored episodes > 250 complexes per minute and > 5 minutes in duration had a high correlation with atrial fibrillation and flutter.     

Analysis of Rabbit Vascular Responses to DBI,an Ingol Derivative Isolated from Euphorbia canariensis

We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries. Concentration-response curves to DBI (10^?8 - 3 × 10^?5 m) were obtained cumulatively in both arteries at resting tension and active tone (KC1, 50 mm). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca²⁺-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10^?4 m) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10^?4 m) inhibited the maximum contraction of the carotid artery to DBI, and completely abolished the response in the basilar artery. In pre-contracted basilar arteries DBI induced a concentration-dependent relaxation that was not modified by incubation with N^G-nitro-l-arginine (l-NOARG; 10^?5 m) or indomethacin (10^?5 m). In the carotid artery with active tone DBI induced further contractions, which were not significantly modified by l-NOARG (10^?5 m) and were potentiated by indomethacin (10^?5 m). These results suggest that DBI contracts rabbit basilar and carotid arteries by a mechanism that is independent of extracellular Ca²⁺ and involves the participation both of protein kinase C and of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism independent of the liberation of nitric oxide and prostacyclin. In the carotid artery prostacyclin but not nitric oxide partially counteracts the contractile action of DBI.     

Familial mandibuloacral dysplasia

A family is described in which two sisters and their two female fifth-cousins were cases of mandibuloacral dysplasia. This syndrome is characterized by mandibular hypoplasia, delayed cranial suture closure, dysplastic clavicles, abbreviated terminal club-shaped phalanges associated with acroosteolysis and atrophy of the skin over hands and feet. Furthermore, in this family alopecia and loss of the lower teeth were noted. We stress the importance of the cutaneous alterations and the possible existence of partial forms of the disease as in one of the patients presented.