Blood pressure on arising, morning blood pressure surge and blood pressure variability in white coat hypertensives and in matched normotensives and sustained hypertensives.

INTRODUCTION: It is still controversial whether subjects with white-coat hypertension (WCHT) exhibit higher cardiovascular risk compared to normotensive subjects (NT). In subjects with WCHT it is not known whether the abnormal blood pressure (BP) reaction in the office also occurs at other times of day, particularly on arising and immediately after waking, i.e. the times at which the majority of cardiovascular events are reported to occur. OBJECTIVE AND METHODS: To evaluate with 24h ambulatory BP measurement the values of morning BP surge, BP on arising and BP variability in subjects with WCHT in comparison with age-, gender- and weight-matched normotensives (BP) and untreated sustained hypertensives (BP). RESULTS: Groups of BP, WCHT and BP were matched for age, gender and body weight: BP: n=69, age 49 +/- 7 years, 54 % female, BMI 26 +/- 1, casual BP 126/79 +/- 5/4 mmHg, daytime BP 124/80 +/- 6/6 mmHg; WCHT: n=74, age 52 +/- 8 years, 57% female, BMI 26 +/- 2, casual BP 152/95 +/- 7/7 mmHg, daytime BP 126/80 +/- 5/6 mmHg; HT: n=79, age 53 +/- 7 years, 56% female, BMI 27 +/- 2, casual BP 154/97 +/- 9/8 mmHg, daytime BP 143/89 +/- 12/10 mmHg. Of the three groups, subjects with WCHT exhibited BP on arising (121/81 +/- 13/8 mmHg) similar to that of NTs (120/80 +/- 13/9 mmHg, NS), both significantly lower than that of HTs (137/92 +/- 17/10 mmHg, p < 0.01), suggesting the absence of an alerting BP reaction in WCHT at that time. By contrast, subjects with WCHT showed higher values of systolic morning BP surge vs. NTs (25 +/- 10 vs. 22 +/- 11 mmHg, p < 0.05), both lower than that observed in hypertensives (33 +/- 11 mmHg, p < 0.01 vs. NT and WCHT) and greater daytime variability (systolic BP standard variation), i.e. 12 2 vs. 10 +/- 2 mmHg, p < 0.05, both lower than that observed in hypertensives (14 +/- 3 mmHg, p < 0.01 vs. NT and WCHT). CONCLUSIONS: Although subjects with WCHT did not show any alerting blood pressure reaction on arising, morning BP surge and BP variability were greater in these subjects than in control normotensives, although lower than sustained hypertensives. Although this is still speculative, we cannot exclude the possibility that even a slight increase in morning BP surge might in the long term constitute an additional load on the circulation that could increase cardiovascular risk in subjects with WCHT compared to matched normotensives.     

Effect of age and maturation on sudomotor nerve regeneration in mice

This study demonstrates that regeneration of unmyelinated sudomotor axons in mice becomes progressively slower during aging. Identical lesions were made in mice aged 0, 2, 4, 6, 7, 24 and 60 weeks. The peroneal, sural and saphenous nerves were cut and tied to prevent regeneration. The sciatic nerve was then frozen at the thigh, leaving the hind paw completely denervated. By 7 days, sweat glands (SGs) of the paw had ceased sweating after pilocarpine injection. Subsequent regeneration of sudomotor axons was judged by the rate of return of pilocarpine sensitivity. SGs in the hind paws of normal newborn mice did not sweat at birth. Cholinergic stimulation first activated sweating at 13 days of life. The number of responsive SGs increased progressively to reach the adult level by 30 days. In one-week-old mice, whose sciatic nerve had been sectioned, the SG response to cholinergic stimulation was very delayed in time and reduced in number. Sweat glands of young mice, between 2 and 4 weeks of age, regained cholinergic sensitivity at a faster rate than mature animals and attained normal SG counts. Throughout a broad intermediate range of age in adulthood (7-24 weeks), the rate of sudomotor nerve regeneration was the same, but in older mice (60 weeks) it was slower and less complete.     

Ruptured aneurysm of the sinus of Valsalva. Presentation of 4 cases and review of the literature

We studied four patients with ruptured aneurysms of the sinus of Valsalva. All were men with a mean age of 33 years. The presenting illness was insidious in three and of abrupt onset in one. Physical examination showed a continuous murmur in all. Chest X ray film showed moderate cardiomegaly. Electrocardiogram disclosed left ventricular hypertrophy. Echocardiogram revealed the site of the rupture which was corroborated by aortography. Two aneurysms ruptured to the right ventricle and two to the right atrium. All were corrected by surgery. All patients became asymptomatic.     

Evaluation of peripheral blood involvement of mantle cell lymphoma by fluorescence in situ hybridization in comparison with immunophenotypic and morphologic findings.

Mantle cell lymphoma is non-Hodgkin's B-cell lymphoma characterized by the t(11;14)(q13;q32) translocation. Peripheral blood involvement of mantle cell lymphoma is usually associated with a poor prognosis and therefore, its identification is clinically important. In this study, we performed cyclin D1/IgH-probe fusion fluorescence in situ hybridization analysis on 223 peripheral blood samples: 185 from 125 mantle cell lymphoma patients, and 38 normal controls. The cutoff values for the test were established using normal controls. Flow cytometry on peripheral blood and corresponding bone marrow samples was used to evaluate this test. In all, 26% of the 185 peripheral blood samples and 27% of the 161 corresponding bone marrow samples were flow cytometry positive for mantle cell lymphoma. The mean numbers of single and- double-fusion signals and the mean number of CD5/CD19-positive cells, absolute blood lymphocyte count, and white blood cell count were significantly higher in peripheral blood and corresponding bone marrow samples with mantle cell lymphoma-positive flow cytometry. Double-fusion signals were more specific than single-fusion ones. Fluorescence in situ hybridization was far more likely to be positive for mantle cell lymphoma when the peripheral blood and the corresponding bone marrow samples had positive flow cytometry results or morphology (P<0.01). Our study indicates that cyclin D1/IgH-fusion fluorescence in situ hybridization analysis could be used to determine the presence and character of circulating mantle cell lymphoma cells in peripheral blood, thus enhancing our ability to evaluate leukemic mantle cell lymphoma and minimum residual disease.     

Non-contact tonometry synchronized with cardiac rhythm and its relationship with blood pressure

PURPOSE: The main objectives of this study were to determine the differences between non-synchronized intraocular pressure (IOP_N) and intraocular pressure readings synchronized with cardiac pulse and try to determine if these parameters are related to blood pressure values. METHODS: One hundred and sixty-five right eyes from 165 volunteers (107 females, 58 males) aged from 19 to 73 years (mean +/- S.D., 29.93 +/- 11.17) were examined with the Nidek NT-4000, a new non-contact tonometer that allows the measurement of IOP synchronized with the cardiac rhythm. IOP measurements in the four different modes of synchronization were taken in a randomized order. Three measures of each parameter were taken and then averaged. The blood pressure was determined three times with a portable manometer and mean values of systolic and diastolic pressure and the pulse rate were computed. Mean arterial pressure (MAP) was determined as being 1/3 of systolic plus 2/3 of diastolic blood pressure. RESULTS: The mean +/- S.D. values for the standard intraocular pressure (IOP_N: 14.76 +/- 2.86), intraocular pressure in the systolic instant or peak (IOP_P: 14.99 +/- 2.85), intraocular pressure in the middle instant between heartbeats or middle (IOP_M: 14.68 +/- 2.76), and intraocular pressure in the diastolic instant or bottom (IOP_B: 13.86 +/- 2.61) were obtained. The IOP_P was higher than the remaining values. A significant difference in mean IOP existed between IOP_B and the remaining modes of measuring (p < 0.05). Differences were statistically significant for all pair comparisons involving IOP_B. Arterial blood pressure values were systolic 125.5 +/- 14.22, diastolic 77.7 +/- 8.38 and MAP 93.64 +/- 9.44 mmHg. The pulse rate was 77.3 +/- 12.6 beats per minute. Except for the MAP (p = 0.025) there was no significant correlation between different IOP values and systolic or diastolic blood pressure, or pulse rate. CONCLUSIONS: NT-4000 is able to differentiate IOP values when synchronized with the cardiac rhythm and those differences are expected to be within a range of +/-2.5 to +/- 3.0 mmHg. IOP_B seems to be the parameter whose value differs from the non-synchronized and the remaining synchronized parameters in a significant way. Other than a weak association with MAP, no significant correlation between IOP and BP was found. The measurements of IOP readings for the three modes are consistent with timings during the cardiac cycle and IOP pulse cycle.     

An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.     

Abnormal movements in Rett syndrome are present before the regression period: a case study.

The suspicion of a diagnosis of Rett syndrome (RTT) is based on clinical criteria that are often not present in the first two stages of the disease, as many of its symptoms will appear at a later age. This sometimes postpones the genetic diagnosis and an early clinical intervention. We present the case of 19-months-old girl who came to the consultation because of an arrest of psychomotor development noticed 5 months earlier without change in sleep pattern, behavior, or social communication. In the observation of 1 hour videotape, she presented subtle stereotypic movements of the face and hands as well as repetitive dystonic posturing of her limbs. A genetic test confirmed the diagnosis of RTT, showing a truncating mutation in the MECP2 gene (R270X). This case confirms that stereotypic movement anomalies, albeit infrequent and subtle, are already present before the regression stage and while maintaining prehension and that, in addition, repetitive dystonic postures may occur. Recognition of these early movement disorders will improve clinicians' ability to perform an earlier diagnosis of RTT.