Cardiovascular responses to angiotensins I and II in normotensive and hypertensive rats; effects of NO synthase inhibition or ET receptor antagonism

1. We compared the cardiovascular responses to angiotensins (I and II), and any possible modulatory influences thereupon of nitric oxide (NO) or endothelin (ET) in conscious male, normotensive, Hannover Sprague-Dawley (SD) rats, and hypertensive, heterozygous ((mRen-2)27), transgenic (TG) rats. 2. The pressor effects of angiotensin I or of angiotensin II were not consistently different in SD and TG rats. The accompanying absolute reductions in renal and mesenteric vascular conductances were smaller in TG rats, but probably due to the baseline vasoconstriction in those animals. 3. Inhibition of NO synthase with L-NAME had no significant effects on the pressor responses to angiotensin I or angiotensin II in either SD or TG rats. L-NAME reduced the absolute, but not percentage, reductions in renal and mesenteric vascular conductances in response to angiotensin I and angiotensin II. L-NAME abolished the hindquarters vasodilator effects of angiotensin I and angiotensin II in both strains of rat. 4. ET receptor antagonism (with SB209670) had no significant influence on the pressor or renal or mesenteric vasoconstrictor effects of angiotensin II in SD rats. In TG rats, the pressor responses to angiotensin II were unaffected by SB209670; the accompanying falls in renal and mesenteric vascular conductances were enhanced in absolute, but not in percentage terms. 5. These results provide no evidence for a buffering action of NO, or a modulatory influence of ET, on the pressor or vasoconstrictor effects of angiotensin I and/or angiotensin II in SD rats. Furthermore, there is no evidence for an altered sensitivity to angiotensin I or angiotensin II, and no evidence for a differential modulatory influence of either NO or ET in TG, compared to SD, rats.     

Striatal neuronal activity during the initiation and execution of hand movements made in response to visual and vibratory cues

Summary Recordings were obtained from 146 neurons in the neostriatum of rhesus monkeys while they performed wrist movements in response to visual and vibratory cues. Of these, 75 putamen and 29 caudate neurons exhibited changes in firing rate that were temporally related to the onset of the wrist movements and that began prior to movement onset. This premovement activity (PMA) usually was directionally specific, in that the magnitude or direction of change in firing rates was different during flexion trials as compared to trials involving wrist extension. PMA onset usually preceded movement onset by more than 100 ms and in most instances preceded the average onset of task-related changes in electromyographic (EMG) activity in muscles of the wrist and forelimb. For most neurons. the changes in neuronal activity that began prior to movement were maintained during movement execution. However, approximately one-third of the neurons that exhibited PMA changed their firing rate in the opposite direction, relative to their PMA and to their baseline rate of activity, once the movement began. Several other neurons either exhibited PMA only or they altered their discharge rates during movement execution but did not exhibit PMA. These observations suggest that, despite the close temporal relationship between the onset of PMA and the onset of wrist movement, the neuronal mechanisms mediating the PMA may differ from those that occur during movement execution. The PMA onset of neostriatal neurons occurred earlier in visually cued than in vibratory cued trials. These differences were statistically significant only for flexion trials, however, in which movements were made against a load and in the same direction as the palmar vibratory stimulus. For trials involving wrist extension, PMA onsets for visually cued as compared with vibratory cued trials were not statistically different. These findings contrast with data obtained previously from somatosensory cortical neurons during performance of the same behavioral task. On average, PMA in the putamen began earlier, relative to movement onset, than it did in the somatosensory cortex. Moreover, in the somatosensory cortex, PMA onset occurred earlier in vibratory cued than in visually cued trials, irrespective of movement direction (Nelson 1988; Nelson and Douglas 1989). For putamen neurons, but not for caudate or cortical neurons, the onset of PMA also occurred significantly earlier during extension trials than flexion trials, irrespective of the modality of the go-cue. These modality-dependent and direction-dependent differences in the PMA onset of neostriatal neurons may reflect the responsiveness of these neurons to somatosensory inputs (e.g., load conditions and vibratory stimulation) that were associated with the behavioral task. These data confirm observations made by other investigators that a substantial proportion of neurons in the putamen exhibit movement-related changes in discharge rate that are initiated prior to task-related changes in EMG activity, and they further suggest that this PMA may be initiated sufficiently early to influence even the earliest task-related activity of cortical neurons.     

Improved techniques in radionuclide imaging of prostatic lymph nodes

Further improvements have been made in the technique of human prostatic lymphoscintigraphy, allowing better anatomical localisation of the areas of uptake of activity. A single median injection into the capsule of 99mTc labelled antimony sulphide colloid has been found to give as good imaging as 2 injections on either side of the midline. By placing markers on the umbilicus, pubic symphysis and both anterior superior iliac spines, a "pelvic grid" can be superimposed on the antero-posterior view. Further help with accurate localisation may be attained by taking 3 views; antero-posterior, postero-anterior and lateral, in 9 instances, prostatic injection was performed without any sedation or anaesthesia. The resulting scintigrams were indistinguishable in quality from those of anaesthetised patients.     

A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

A qualitative analysis of patients’ perception of microwave endometrial ablation as a satisfactory treatment for heavy menstrual blood loss

To explore and analyse patients’ views and comments on microwave endometrial ablation (MEA), we designed a simple and concise questionnaire of 10 items that the participants answered by ticking boxes. They were invited to add their own comments and opinions if they wished. The questionnaire survey was posted to 470 patients who were treated with MEA at Derriford Hospital between 1997 and 2003. We received replies from 343 patients (73%), of whom 165 included handwritten comments (48%). These were reviewed using content thematic analysis. This paper describes the findings of this analysis. Of the 343 respondents, 127 expressed their satisfaction, 32 would recommend MEA to others, and 17 claimed that MEA had transformed their lives. They used words such as “delighted,” “grateful,” “fantastic,” “I cannot tell you how wonderful it has been,” “freedom at last,” “I feel so much better within myself,” “I cannot begin to describe the feelings of well-being and relief I have experienced since I had this treatment,” and “it has changed my life from being housebound to never giving my periods a thought.” Thirty-eight patients were not satisfied; of these, 14 were experiencing moderate to severe pain, and six claimed to have developed severe pain de novo. Their comments included “I was disappointed MEA did not work for me” and “I get heavy bleeding and pain each month, [whereas] before I had no period pains at all.” In conclusion, MEA has been a “miracle cure” for many women who responded, with around 77% being satisfied with this treatment. For a small number, MEA was not successful. For some women, pain was a problem that either developed de novo or was preexisting in the form of dysmenorrhoea. In this paper we also mention success rates and figures from quantitative studies, and we recommend including quotes from satisfied patients in patient information leaflets to further help women and their physicians make informed choices about managing heavy menstrual blood loss, particularly when medical treatment is known to be less successful and with some women being concerned about its side effects.Shortly after this paper was submitted, Emad Louis tragically died from complications following surgery, whilst waiting to take up his post as a Consultant at St. Mary’s Hospital, Isle of Wight. We remember him with great affection as a wonderful colleague, who is held in the highest regard by his patients and all who worked with him. He is greatly missed.He leaves a wife and son who are enormously proud that his research has been published.