Long-term seton drainage for high anal fistulas in Crohn's disease—A sphincter-saving operation?

METHODS: Forty-one consecutive patients with Crohn's disease who underwent long-term seton drainage for high transsphincteric, suprasphincteric, or extrasphincteric anal fistula from 1985 to 1993 were reviewed. The subsequent associated procedure was simple seton removal (18), secondary fistulotomy (7), rectal flap advancement (3), and proctectomy (2). Eleven patients still had the seton in place. RESULTS: Recurrence developed in seven patients (39 percent) undergoing simple seton removal and in one patient undergoing rectal flap advancement. None of the patients treated by secondary fistulotomy developed a recurrence. At the end of follow-up, five patients (12 percent) required proctectomy mainly for severe proctitis, and five patients (12 percent) developed anal incontinence, which was severe in two. CONCLUSION: Long-term seton drainage for high anal fistula in Crohn's disease is efficacious in both treating sepsis and preserving anal sphincter function.     

The effect of exercise training in symptomatic patients with grown-up congenital heart disease: a review

Introduction: The number of grown-up congenital heart disease (GUCH) patients is steadily increasing. Unfortunately, the majority of these patients suffer from late sequelae, with heart failure being the most common cause of death. Exercise training is beneficial and safe in patients with acquired heart failure, as well as in asymptomatic GUCH patients. However, its effect remains unknown in symptomatic GUCH patients. This could cause reticence on positive sports advice, with possible counterproductive effects.

Areas covered: A review of current literature was performed to evaluate the effect of exercise training in symptomatic (NYHA≥2) GUCH patients. The search yielded a mere three studies including symptomatic patients, and another six studies including also patients in NYHA 1 without making clear distinction between the NYHA subgroups.

Expert commentary: Suboptimal trial designs, low patient numbers, and homogeneity of investigated cardiac anomalies make this review insufficient to draw definite conclusions. However, all studies describe overall positive effects of exercise training in symptomatic GUCH patients in terms of exercise capacity and quality of life. There were no safety concerns. Larger-scaled, randomized controlled trials are needed to obtain certainty.     

Post-exposure prophylaxis after occupational and non-occupational exposures to HIV: an overview of the policies implemented in 27 European countries

The aim of this survey, which was part of an English-French project supported by the Commission of the European Communities, was to compare access to HIV post-exposure prophylaxis (PEP) in the occupational and non-occupational contexts in 27 European countries. A protocol was designed in May 1998 in collaboration with all country consultants. Data were collected at country level by each consultant through interviews, review of local and national recommendations and results of national or local surveys. The final comparative analysis was carried out from the individual country reports and a review of the literature. The large majority of European countries have detailed procedures regarding occupational PEP: 20/27 have produced national guidelines, three have adopted the US CDC recommendations and only four have no official recommendations. Although no standard protocol exists, the more common one is a four-week implementation of a triple combination therapy. In the context of non-occupational exposure to HIV, only five countries have guidelines with specific recommendations and one country has adopted the CDC recommendations. In the majority of cases (13 countries), PEP is never recommended but is only available in a few circumstances, sometimes with major limitations. In the last eight countries, such PEP is not currently available. Although the estimations of HIV transmission risks in occupational and non-occupational contexts are really comparables, easy access to PEP after accidental sexual or blood exposures is not guaranteed for the general population in the majority of European countries.     

Leka, a New Platelet Antigen Absent in Glanzmann''s Thrombasthenia

The serum of a patient who developed a posttransfusion purpura contained antibodies directed against a previously undescribed platelet antigen Lek a. The antiplatelet activity was present in the IgG fraction and was detected by immunofluorescence, 51Cr lysis and 14C-serotonin release. The frequency of the Lek a phenotype in the French population is 98.18%. Lek a does not appear to be sex-linked and seems to be closely related to the Bak a antigen. The Lek a antigen is not expressed on thrombasthenic platelets but is found on platelets from patients with the Bernard-Soulier syndrome which suggests that this antigen is carried by platelet glycoproteins IIb and/or IIIa.     

Cytogenetic analysis of metastatic effusions from breast tumors

Chromosome analysis was performed on direct and in vitro cultures of 30 effusions from breast carcinoma. Although in 14 samples normal diploid stem-lines were found, chromosome abnormalities were present in stem- or side-lines of all cases. Recurrent numerical deviations were only verified as gains of Nos. 6 and 7. Rearrangements were seen involving almost all chromosome pairs (except No. 18 and gonosomes), however, Nos. 1, 3, 6 and 11 were those most frequently related to the genesis of markers. Double minutes (DMs) were found in seven samples, and there was a homogeneously staining region (HSR) in one.     

Anomalous origin of the left coronary artery. The form in infants

Twenty-four cases of anomalous origin of the left coronary artery from the pulmonary artery are reported. These cases were collected over 27 years divided into three 9-year periods according to the years of the initial studies. The clinical aspects and diagnostic investigations (notably echocardiography, myocardial radioisotope imaging and various angiographic procedures) are reviewed; aortography seems to be, even now, the best exploratory method. Treatment is analyzed according to the periods of observations. From the earliest cases it may be concluded that ligation proved ineffective in infants and medical treatment often failed. Progressively, medical treatment with digitalis (now better controlled), potassium-sparing diuretics and vasodilators has become more effective. On the other hand, direct reimplantation of the left coronary artery onto the aorta has become the preferred surgical procedure. Among the 8 most recent cases (seen between 1977 and 1986), 4 were cured by medical treatment under the age of 3 and subsequent reimplantation. In the other 4 patients asystolia responded to medical treatment, and these children are now awaiting reimplantation.     

An epidemiological study of malaria in Bioko and Annobón islands (Equatorial Guinea).

A seroparasitological study of malaria was carried out in two of the more important islands of Equatorial Guinea, Bioko (ex Fernando Poo) and Annobón. The study involved a randomly-chosen population of children aged from two to nine years. In Bioko 1130 children were chosen from 29 of the 51 villages on the island; in Annobón 185 children were chosen from the capital town, where all the population lived. Indirect immunofluorescence tests (IFAT) showed a prevalence of malaria infection of 29.8% in Bioko and 55.7% in Annobón. The parasitic prevalence (malaria index) was 26.6% and 55.1% respectively, and the splenic index was 57.0% and 54.6% respectively. The results indicate that this is an area of stable hyperendemic malaria, which may benefit from an antimalarial programme.     

Hydrolysis of Clavulanate by Mycobacterium tuberculosis β-Lactamase BlaC Harboring a Canonical SDN Motif

Combinations of β-lactams with clavulanate are currently being investigated for tuberculosis treatment. Since Mycobacterium tuberculosis produces a broad spectrum β-lactamase, BlaC, the success of this approach could be compromised by the emergence of clavulanate-resistant variants, as observed for inhibitor-resistant TEM variants in enterobacteria. Previous analyses based on site-directed mutagenesis of BlaC have led to the conclusion that this risk was limited. Here, we used a different approach based on determination of the crystal structure of β-lactamase Bla_MAb of Mycobacterium abscessus, which efficiently hydrolyzes clavulanate. Comparison of Bla_MAb and BlaC allowed for structure-assisted site-directed mutagenesis of BlaC and identification of the G¹³²N substitution that was sufficient to switch the interaction of BlaC with clavulanate from irreversible inactivation to efficient hydrolysis. The substitution, which restored the canonical SDN motif (SDG→SDN), allowed for efficient hydrolysis of clavulanate, with a more than 10⁴-fold increase in k_cat (0.41 s⁻¹), without affecting the hydrolysis of other β-lactams. Mass spectrometry revealed that acylation of BlaC and of its G¹³²N variant by clavulanate follows similar paths, involving sequential formation of two acylenzymes. Decarboxylation of the first acylenzyme results in a stable secondary acylenzyme in BlaC, whereas hydrolysis occurs in the G¹³²N variant. The SDN/SDG polymorphism defines two mycobacterial lineages comprising rapidly and slowly growing species, respectively. Together, these results suggest that the efficacy of β-lactam–clavulanate combinations may be limited by the emergence of resistance. β-Lactams active without clavulanate, such as faropenem, should be prioritized for the development of new therapies.