Radiation following percutaneous balloon aortic valvuloplasty to prevent restenosis (RADAR pilot trial).

OBJECTIVES: We wished to determine the feasibility and early safety of external beam radiation therapy (EBRT) used following balloon aortic valvuloplasty (BAV) to prevent restenosis. BACKGROUND: BAV for calcific aortic stenosis (AS) has been largely abandoned because of high restenosis rates, i.e., > 80% at 1 year. Radiation therapy is useful in preventing restenosis following vascular interventions and treating other benign noncardiovascular disorders. Methods: We conducted a 20-patient, pilot study evaluating EBRT to prevent restenosis following BAV in elderly patients with calcific AS. Total doses ranging from 12-18 Gy were delivered in fractions over a 3-5 day post-op period to the aortic valve. Echocardiography was performed pre and 2 days post-op, 1, 6, and 12 months following BAV. RESULTS: One-year follow-up is completed (age 89 +/- 4). There were no complications related to EBRT. Eight patients died prior to 1 year; 5 of 10 (50%) in the low-dose (12 Gy) group and 3 of 10 (30%) in the high-dose (15-18 Gy) group. None of these 8 patients had restenosis, i.e., > 50% loss of the initial AVA gain, and only three deaths were cardiac in origin. One patient underwent aortic valve replacement and none repeated BAV. By 1 year, 3 of the initial 10 (30%) in the low-dose group and 1 of 9 (11%) in the high-dose group demonstrated restenosis (21% overall). CONCLUSIONS: EBRT following BAV in elderly patients with AS is feasible, free of early complications, and holds promise in reducing the 1 year restenosis rate in a dose-dependent fashion.     

Increased prevalence of cytomegalovirus antibodies in homosexual men with syphilis: relation to sexual behaviour

Serum samples from 146 homosexual males, 40 heterosexual males and 51 females with at least one episode of syphilis were tested for the presence of IgG and IgM antibodies against cytomegalovirus (CMV IgG and CMV IgM). 100 blood donors served as a control group. CMV IgG was present in 95% of homosexual men compared with 68% of heterosexual men (p less than 0.001) and 73% of females (p less than 0.001) with past or present syphilis. CMV IgM was found in 43-68% of the venereal patients and with the highest percentage in homosexual men. Only 7% of blood donors had CMV IgM. It is concluded that CMV infection may be regarded as a venereal disease.     

Inhibition of gastric acid secretion by jejunal glucose and its relation to osmolality and glucose load

Intrajejunal infusion of hypertonic glucose and hypertonic saline inhibits pentagastrin-stimulated gastric acid secretion in man. This effect is generally ascribed to the hyperosmolality of the solutions. Five volunteers were given 50 g glucose in osmolar concentrations of 2700 mosmol/l and 900 mosmol/l, and five were given 25 g glucose in osmolar concentrations of 2700 mosmol/l and 300 mosmol/l. Control studies with intrajejunal infusion of physiologic saline were performed in all subjects. Median inhibition of gastric acid secretion was 91% after 50 g glucose and 47% after 25 g glucose and was unrelated to the osmolar concentration. These findings suggest that the acid-inhibitory effect of intrajejunally administered glucose is related to the glucose load and not to the osmolar concentration. Plasma responses of intact neurotensin, immunoreactivity, NH2-terminal neurotensin immunoreactivity, enteroglucagon, and gastric inhibitory polypeptide were all related to the amount of glucose given. Glucagon and somatostatin, both of which are potent inhibitors of gastric secretion, were not released by intrajejunally administered glucose.     

Human placental lactogen concentration during physiological fluctuations of serum glucose in normal pregnant and gestational diabetic women.

Oral glucose tolerance tests (OGTT) were carried out in 9 normal pregnant women and 11 non-obese gestational diabetics in late pregnancy. All samples were analysed for the content of glucose, insulin and placental lactogen hormone (HPL). Furthermore, spontaneous changes in the serum HPL concentration during a 3 h period were studied in 6 normal women in the 2nd half of pregnancy. During OGTT only small and insignificant changes in the level of HPL were observed in both the normal subjects and the gestational diabetics. Furthermore, the mean HPL concentration curves of the normal subjects and the gestational diabetics were superimposed although the mean glucose concentration curves were significantly different. The study of spontaneous changes in HPL revealed only small and insignificant fluctuations in the serum HPL level, and the mean concentration curve resembled those obtained from the OGTT-study. It is concluded that neither the absolute serum glucose level, nor physiological fluctuations in the serum glucose concentration seemed to influence the serum concentration of HPL in this type of patients.     

Feasibility of transcatheter intervention for severe aortic stenosis in patients >or=90 years of age: aortic valvuloplasty revisited.

OBJECTIVES: The goals of this study were to determine the feasibility, safety, and early outcomes of balloon aortic valvuloplasty (BAV) for severe aortic stenosis in a nonagenarian population. BACKGROUND: This very elderly population is expanding rapidly, has a high incidence of aortic stenosis, and uncommonly undergoes surgical aortic valve replacement. These patients may best be treated with a transcatheter approach due to comorbidities, surgical risk, and personal preference. METHODS: We reviewed 31 consecutive patients >or=90 years of age who underwent BAV at our institution from July 2003 to August 2006 for data pertinent to patient characteristics, procedural techniques, and 30-day outcomes. RESULTS: Our patients had a mean age of 93 +/- 3.0 years (90-101). The society of thoracic surgery risk score was 18.5 (+/-10.2) and logistic Euroscore was 35.8 (+/-19.3). Twenty-five patients (81%) underwent retrograde BAV and 6 (19%) antegrade BAV. Five patients (16%) underwent combined BAV and coronary stenting. Overall mean aortic valve area increased from 0.52 cm2 (+/-0.17) to 0.92 cm2 (+/-0.22) and mean New York Heart Association (NYHA) functional class improved from 3.4 to 1.8. Intraprocedural mortality occurred in one patient (3.2%) and 30-day mortality in three patients (9.7%). CONCLUSIONS: BAV can be carried out in high risk nonagenarian patients with an acceptable complication rate, low perioperative mortality, and early improvement in NYHA functional class.     

Complete histological regression of Kaposi's sarcoma following treatment with protease inhibitors despite persistence of HHV-8 in lesions

There is no current curative treatment for HIV-related Kaposi's sarcoma. The identification of human herpesvirus-8 as a possible aetiological agent suggests potential efficacy of anti-viral agents. We report here on the complete histological remission of Kaposi's sarcoma following treatment with protease inhibitors, even in patients with limited virological response and persistence of HHV-8.     

Metabolite ratios as potential biomarkers for type 2 diabetes: a DIRECT study

Aims/hypothesis

Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes.

Methods

We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders.

Results

There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p < 9.2 × 10^?7). These associations were significantly stronger compared with the individual metabolite components. One of the ratios, valine to phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2), in addition showed a directionally consistent positive association with OGTT-derived measures of insulin secretion and resistance (p ≤ 5.4 × 10^?3) and prevalent type 2 diabetes (OR_{Val_PC ae C32:2} 2.64 [β 0.97 ± 0.09], p = 1.0 × 10^?27). Furthermore, Val_PC ae C32:2 predicted incident diabetes independent of established risk factors in two epidemiological cohort studies (HR_{Val_PC ae C32:2} 1.57 [β 0.45 ± 0.06]; p = 1.3 × 10^?15), leading to modest improvements in the receiver operating characteristics when added to a model containing a set of established risk factors in both cohorts (increases from 0.780 to 0.801 and from 0.862 to 0.865 respectively, when added to the model containing traditional risk factors + glucose).

Conclusions/interpretation

In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.

     

The short-term repeatability of histamine bronchial testing in young males. The SUS study

We have measured bronchial responsiveness (BR) to histamine on two occasions between 5 and 24 h apart, to determine if conventional and new indices of BR are repeatable. A random sample of 29 healthy male subjects with a mean age of 19 (SD 3.44) years from a larger study repeated a Yan method test of BR, recording both partial and maximal expiratory flow volume (PEFV and MEFV) curves. From the MEFV curves log-dose slopes (LDS) for forced expiratory volume in 1 sec (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity (FVC) (FEF(25-75%)), mean expiratory flow at 30% and 40% of FVC (MEF30, MEF40), and the first moment of the spirogram (alpha1) truncated at 75% and 90% of FVC were calculated, as well as the provocative dose that induces a 20% fall in FEV1 (PD20FEV1). From the PEFV curves LDS for alpha(1)75% and alpha(1)90%, and MEF30 and MEF40 were derived. Apart from MEF30 and alpha(1)90% the second test was significantly lower (P<0.05) than the first when measuring the repeatability of spirometric indices, whereas the LDS of the indices showed no significant change. The repeatability expressed as intra-class correlation coefficient (ICC) was highest for LDS FEV1 (0.87), second highest for LDS MEF40 (0.67) and LDS MEF30 (0.65). The LDS for moment indices were much less repeatable and the lowest ICC was found in all LDS indices derived from PEFV curves. Within-subject variance was not influenced by atopic status, smoking habits or recordable PD20FEV1. As tests for bronchial hyper-responsiveness (BHR) the LDS of FEV1, MEF40 and MEF30 seem to be acceptable for use in population studies.