Abnormal blood-pressure response to exercise and oxygen consumption in patients with hypertrophic cardiomyopathy

Background Abnormal blood-pressure response during exercise occurs in about one third of patients with hypertrophic cardiomyopathy (HCM), and it has been associated with a high risk of sudden cardiac death. We assessed the hemodynamics of exercise in HCM patients with abnormal blood-pressure response by using ambulatory radionuclide monitoring (VEST) of left-ventricular (LV) function, and exercise tolerance by oxygen consumption. Methods Twenty-two HCM patients uderwent treadmill exercise during VEST monitoring. A cardiopulmonary exercise test was performed a few days after. The VEST data were averaged for 1 minute. Stroke volume, cardiac output, and systemic vascular resistance were expressed as percent of baseline. Exercise tolerance was assessed as maximal oxygen consumption. Results In eight HCM patients (36%) with an abnormal blood-pressure response, endsystolic volume increased more (52%±21% vs 31%±28%, P=.012), and the ejection fraction (−31%±17% vs−14%±22%, P=.029) and stroke volume (−21%±21% vs 3%±28%, P=.026) fell more, than in patients with normal response. Cardiac output increased less in the former patients (49%±44% vs 94%±44%, P=.012). Systemic vascular resistance decreased similarly, irrespective of blood-pressure response (−28%±26% vs −34%±26%. P=N.S.). Percent of maximal predicted oxygen consumption was lower in HCM patients with an abnormal blood-pressure response (63%±11% vs 78%±15%, P=.025). Conclusions In HCM patients, abnormal blood-pressure response was associated with exercise-induced LV systolic dysfunction and impairment in oxygen consumption. This may cause hemodynamic instability, associated with a high risk of sudden cardiac death.     

Impact of inducible ischemia by stress SPECT in cardiac risk assessment in diabetic patients: rationale and design of a prospective, multicenter trial.

BACKGROUND: A prospective, multicenter trial has been designed to evaluate the impact of inducible ischemia by stress single photon emission computed tomography (SPECT) in diabetic patients and to define the role of SPECT in assessing the cardiac risk in such patients. This report presents the details and implications of the Impact of Inducible Ischemia by Stress SPECT (IDIS) trial design. METHODS AND RESULTS: Between January 2002 and September 2005, 1006 consecutive patients (649 men and 357 women; mean age, 63 +/- 9 years) with at least a 5-year history of type 2 diabetes mellitus were enrolled. All patients underwent stress-rest sestamibi SPECT imaging with physical exercise (n = 573) or dipyridamole (n = 433). SPECT studies will be analyzed by use of a 17-segment scoring system to calculate left ventricular ejection fraction, summed stress score, summed rest score, and summed difference score. The SPECT study will be considered abnormal if the summed stress score is 3 or greater. Patients with abnormal studies will be considered to have ischemia if the summed difference score is 2 or greater. CONCLUSION: The results of this trial should help to define the role of SPECT in assessing cardiac risk in diabetic patients. Furthermore, this trial will prospectively evaluate subsequent patient outcome during long-term follow-up.     

In vivo RANK signaling blockade using the receptor activator of NF-kappaB:Fc effectively prevents and ameliorates wear debris-induced osteolysis via osteoclast depletion without inhibiting osteogenesis.

Prosthesis failure due to wear debris-induced osteolysis remains a major clinical problem and the greatest limitation for total joint arthroplasty. Based on our knowledge of osteoclast involvement in this process and the requirements of receptor activator of NF-kappaB (RANK) signaling in osteoclastogenesis and bone resorption, we investigated the efficacy of RANK blockade in preventing and ameliorating titanium (Ti)-induced osteolysis in a mouse calvaria model. Compared with placebo controls we found that all doses of RANK:Fc above 1 mg/kg intraperitoneally (ip) per 48 h significantly inhibited osteoclastogenesis and bone resorption in response to Ti implanted locally. Complete inhibition occurred at 10 mg/kg ip per 48 h, yielding results that were statistically equivalent to data obtained with Ti-treated RANK-/- mice. We also evaluated the effects of a single injection of RANK:Fc on day 5 on established osteolysis and found that Ti-treated were still depleted for multinucleated tartrate-resistant acid phosphatase-positive (TRAP+) cells 16 days later. More importantly, this osteoclast depletion did not affect bone formation because the bone lost from the osteolysis on day 5 was restored by day 21. An assessment of the quantity and quality of the newly formed bone in these calvariae by calcein labeling and infrared (IR) microscopy, respectively, showed no significant negative effect of RANK:Fc treatment. These studies indicate that osteoclast depletion via RANK blockade is an effective method to prevent and reverse wear debris-induced osteolysis without jeopardizing osteogenesis.     

Quantification of erythema using digital camera and computer-based colour image analysis: a multicentre study

Background/purpose Colour measurements obtained from digitized images have been proposed as a simple and cost-effective way to evaluate skin colour and the activity of treatments. The main disadvantage of the method is the fact that it is highly dependent on ambient light: even if an accurate control of subjects' illumination is provided, readings remain not comparable among different laboratories. The purpose of this study was to develop a highly reproducible system for computerized colour image analysis of skin erythema, making it possible to compare readings from different environmental light conditions. Patients and Methods Three hundred and forty-eight Caucasian adult healthy subjects (age range: 18–60 years) of both sexes (14% males, 86% females), were enrolled in the study by 49 dermatologists distributed all over Italy. They were recruited among patients who required aesthetic treatments involving skin erythema, like chemical peeling and laser epilation. Once the treatment was administered, clinical evaluations and pictures were taken at the level of treated areas. Visual assessment of erythema was done on the basis of conventional clinical grades (0 = absent; 1 = slight; 2 = moderate; 3 = intense). The clinicians participating in the study were asked to put a standard colour marker (red, green and blue coloured self-adhesive ring) in the photographed skin area. The difference between r, g, b values of photographed colour markers on the skin of single patients participating in the study and the r, g, b values obtained photographing the colour marker in fixed illumination conditions was used to adjust skin colour measurements. Then erythema index (E.I) on digitized images was calculated subtracting red value to green one by averaging procedure of different pixels. Results Erythema index. average value among the groups divided according to the conventional clinical score increased progressively from score 0–2, while it decreased from score 2 to score 3. The differences in E.I. mean values among the score groups (0 vs. 1, 1 vs. 2, 2 vs. 3) were statistically significant (P < 0.05). Conclusion We developed a method for the measurement of skin erythema using digital camera, normalized r, g, b colour co-ordinate system and computerized calculation of E.I. Clinical usefulness of our method for absent, slight and moderate erythema, was demonstrated. For intense erythema lesions we did not find a correspondence between clinical and computerized evaluation, probably due to other factors involved in skin inflammation (e.g. oedema).     

Validity of self–reported hysterectomy and tubal sterilisation

Abstract: Both hysterectomy and tubal sterilisation offer significant protection from ovarian cancer, and the risk of cardiovascular disease in women is lowered after hysterectomy. Since little is known about the accuracy of women's self–reports of these procedures, we assessed their reliability and validity using data obtained in a case–control study of ovarian cancer. There was 100 per cent repeatability for both positive and negative histories of hysterectomy and tubal sterilisation among a small sample of women on reinterview. Verification of surgery was sought against surgeons' or medical records, or if these were unavailable, from randomly selected current general practitioners for 51 cases and 155 controls reporting a hysterectomy and 73 cases and 137 controls reporting a tubal sterilisation. Validation rate for self–reported hysterectomy against medical reports (32 cases, 96 controls) was 96 per cent (95 per cent confidence interval (CI) 91 to 99) and for tubal sterilisation (32 cases, 77 controls) it was 88 per cent (CI 81 to 93), which is likely to be an underestimate. Although findings are based on small numbers of women for whom medical reports could be ascertained, they are consistent with other findings that suggest women have good recall of past histories of hysterectomy and tubal sterilisation; this allows long–term effects of these procedures to be studied with reasonable accuracy from self–reports.     

Cyclooxygenase‐2 in oligodendroglioma: Possible prognostic significance

Cyclooxygenase‐2 (COX‐2) is the inducible form of the enzyme involved in the first two steps of the prostaglandins and thromboxane synthesis. Up‐regulation of COX‐2 is demonstrated in tumors where it can modulate tumoral progression, metastasis, multidrug resistance and angiogenesis. Selective COX‐2 inhibitors are seen with growing interest in the tumors treatment. This present study reviews the COX‐2 expression in 32 primary oligodendrogliomas (24 WHO II; eight WHO III) and two glioblastomas with prominent oligodendroglial features (WHO IV). Immunohistochemical results were compared with survival in order to verify the COX‐2 prognostic significance. COX‐2 positivity was found in 44% tumors. Median survival of the patients with a COX‐2 positive lesion was 37 months; median survival of the patients with a COX‐2 negative lesion was 93 months (P = 0.010). Twenty‐nine percent WHO grade II tumors, 87% WHO grade III, 50% WHO grade IV resulted COX‐2 positive (P = 0.016). In patients affected by WHO grade II oligodendroglioma, median survival was 24 and 96 months, respectively, in COX‐2 positive and negative lesions (P = 0.012). In conclusion, even if further studies on different, homogeneous and larger series in vivo are certainly necessary, it is believed that COX‐2 could really have a prognostic value and can be considered as a possible therapeutic opportunity.     

Mevalonate kinase genotype in children with recurrent fevers and high serum IgD level

In selected cases, childhood’s recurrent fevers of unknown origin can be referred to systemic autoinflammatory diseases as mevalonate kinase deficiency (MKD), caused by mutations in the mevalonate kinase gene (MVK), previously named “hyper-IgD syndrome” due to its characteristic increase in serum IgD level. There is no clear evidence for studying MVK genotype in these patients. From a cohort of 305 children evaluated for recurrent fevers in our outpatient clinic during the decade 2001–2011, we have retrospectively selected 10 unrelated Italian children displaying febrile episodes, associated with recurrent inflammatory signs (variably involving gastrointestinal tube, joints, lymph nodes, and skin) and persistently increased serum IgD levels. All these patients were examined for MVK genotype: only 2 presented bonafide MVK mutations, 5 showed the same S52N MVK polymorphism, while the remaining 3 had a wild-type MVK sequence. Clinical details of these patients have been reviewed through the critical analysis of their medical charts. Our report underscores the pitfalls of MKD diagnosis based on clinical grounds and IgD levels, emphasizing the uncertain contribution of MVK polymorphisms in the diagnostic assessment of the syndrome.     

Reduced pineal volume in male patients with schizophrenia: no relationship to clinical features of the illness

Several investigations have suggested pineal gland abnormalities in the pathogenesis of schizophrenia. The pineal volume on brain magnetic resonance imaging scans was calculated in 15 male schizophrenic inpatients and in 16 matched control subjects. The statistical comparison found a significant difference of pineal gland volume between schizophrenics and controls (P = 0.022), with a smaller pineal volume in the schizophrenics. These results do not confirm the previous data of Schizophrenia Res. 14 (1995) 253, showing no significant pineal volumetric differences between schizophrenics and normal controls. Since the present study is based on a smaller but more homogeneous sample of patients, this could reduce the heterogeneity features of the schizophrenic disease. No correlation was found between pineal volume and clinical and psychopathological features of the schizophrenic subjects. Volume reduction in schizophrenia could be at least partially included in the wider brain developmental abnormalities of the illness or in the late effects of previous neuroleptic treatments.