Effects of the cold pressor test on short-term fluctuations of finger arterial blood pressure and heart rate in normal subjects

The effect of the cold pressor test on autonomic cardiovascular control was studied non-invasively by means of spectrum analysis of periodic heart rate and blood pressure fluctuations in ten normal subjects. Fast Fourier Transform algorithm based on a 256-point time series (sampling rate 2 Hz, i.e. 2-min and 8-s) was used to estimate the amplitude spectra of heart rate and blood pressure rhythmicity at the low frequency (70–140 mHz) and respiration related frequency (230–270 mHz) band. Respiration rate was controlled at 250 mHz. Auto- and cross-spectral techniques were used to determine the complex relationship between systolic blood pressure and heart rate fluctuations in the frequency domain. The spectral pattern of systolic and diastolic blood pressure showed a marked increment of the absolute and relative (100 multiplied with absolute value/total area under the curve of the amplitude spectrum from 15–500 mHz) low frequency component: control vs. cold pressor test—systolic blood pressure—absolute values (in [mmHg/Hz^1/2]): 634.4 ± 48.9 vs. 827.4 ± 69.9* relative values (in [%]): 26 ± 2 vs. 32 ± 2*; diastolic blood pressure —absolute values: 433.2 ± 42.3 vs. 537.2 ± 45.8* relative values: 35 ± 3 vs. 40 ± 2*, (average ± SEM, *P < 0.05). The cold pressor test induced no change in average heart rate; the absolute low frequency component in heart rate spectra increased clearly during the test: low frequency component (in [bpm/Hz^1/2]): 586.9 ± 89.9 vs. 712.0 ± 91.4*, while the relative low frequency component did not change: 29 ± 3 vs. 30 ± 3. There was no alteration in the respiration related frequency component in all time series and in the transfer gain and phase functions during cold pressor test. We conclude that the cold pressor test increases low frequency systolic blood pressure fluctuations which reflects an increase in sympathetic vasomotor control. Furthermore the cold pressor test does not induce change in the transfer gain and phase characteristics of modulation of heart rate by systolic blood pressure.     

An effective strategy for diagnosing occupational asthma: use of induced sputum

Monitoring airway inflammation by means of induced sputum cell counts seems to improve the management of asthma. We sought to assess whether such monitoring at the end of periods at and away from work combined with the monitoring of PEF could improve the diagnosis of occupational asthma. We enrolled subjects suspected of having occupational asthma. Serial monitoring of PEF was performed during 2 weeks at and away from work. At the end of each period, induced sputum was collected. Specific inhalation challenge was subsequently performed. PEF graphs were interpreted visually by five independent observers. Forty-nine subjects, including 23 with positive specific inhalation challenge, completed the study. The addition of sputum cell counts to the monitoring of PEF increased the specificity of this test, respectively, by 18 (range [r] 13.7-25.5) or 26.8% (r 24.8-30.4) depending if an increase of sputum eosinophils greater than 1 or 2% when at work was considered as significant. The sensitivity increased by 8.2% (r 4.1-13.4) or decreased by 12.3% (r 3.1-24.1) depending on the cutoff value in sputum eosinophils chosen (greater than 1 or 2%, respectively). The addition of sputum cell counts to PEF monitoring is useful to improve the diagnosis of occupational asthma.     

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.     

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.     

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.