By X. Sven. Carrol University. 2018.
Modiﬁed from Meunier discount prevacid 15mg amex, Pierrot-Deseilligny & Simonetta (1993) cheap prevacid 15mg with mastercard, with permission 30 mg prevacid with mastercard. Methodology 75 10 (b) 10 (c) Sciatic 1 x MT (a) 0 0 Bi 29 33 37 41 29 33 37 41 MN 10 (d ) 10 (e) GM 1 x MT GM Ia Bi MN 0 0 10 (f ) 10 (g) GM 0 order prevacid 15 mg overnight delivery. Low electrical threshold for monosynaptic Ia excitation from gastrocnemius medialis to biceps femoris. The difference in latencies of the homonymous and heteronymous peaks corresponds to the difference in afferent conduction times. Modiﬁed from Meunier, Pierrot-Deseilligny & Simonetta (1993), with permission. Low electrical threshold Tendon tap When the connection is strong, its electrical thresh- old is as low as that of homonymous monosynaptic Heteronymousmonosynapticexcitationmayalsobe Ia excitation (Meunier, Pierrot-Deseilligny & Simon- produced by a tendon tap which, at rest, strongly etta, 1993). This corresponds to the duced by electrical stimulation ((h ), 1 × MT) and by 76 Monosynaptic Ia excitation 175 (b) Median 0. Increasing the electrical threshold for median-induced monosynaptic Ia excitation of biceps brachii motoneurones by prolonged vibration to the tendon of ﬂexor carpi radialis. Thefacilita- High-frequency vibration constitutes a potent sti- tion appeared at the –4. At this In the cat prolonged vibration raises the electrical early ISI, the threshold for the facilitation was signi- threshold of the responding Ia afferents because it ﬁcantly increased (Fig. Methodology 77 Absence of early excitation from charge is not occluded by the antidromic motor vol- cutaneous afferents ley. The question then arises what is the range of the electrical thresholds of Ia afferents in humans when In the human upper limb, the conduction velocity stimulating nerves through surface electrodes. It is therefore important Growth of heteronymous that cutaneous stimulation that evoked the same Ia monosynaptic excitation sensationsaselicitedbythemixednervestimulation The growth of the Ia EPSPs has been estimated in the failed to reproduce the early peak of Ia excitation (as PSTHs of single motor units as the stimulus inten- in the experiment illustrated in Fig. The most became clearer at 2–3 × MT at a latency of 31 ms cogentargumentsaredrawnfromexperimentsusing ((d )–(g )), and increased further at 4–5 × MT, associ- bidirectional connections where the conclusions do ated with a decrease in latency to 30. Similar results were found with the femoral-induced Notwithstanding this, strong evidence is also pro- excitation of tibialis anterior units and the superﬁ- videdbyexperimentsshowingthatthedifferencesin cial peroneal excitation of soleus units. Given a threshold for Ia afferents of mous excitation is supported by (i) a low electrical ∼0. The mean decrease in latency of the monosynaptic peak relative to the latency at 1 × MT is plotted against the stimu- Range of electrical thresholds of lus intensity in M. Ia afferents when stimulating The decrease in latency is probably due to two using surface electrodes phenomena: stimulation of the afferents at more proximal nodes as stimulus intensity increased, so When stimulating peripheral nerves directly, as in producing an effectively shorter afferent path, and cat experiments, the stimulus strength has to be a more rapidly rising EPSP as more group I affer- increasedtotwicethethresholdofthemostexcitable ents were recruited. The latter has been shown in afferents to set up a maximal group I volley (Brock, the cat to produce a decrease in the latency of the Eccles & Rall, 1951). Given a threshold for human Ia corresponding peak in the PSTH of up to 0. However, ingwouldbeexpectedinhumansbecausetheextent in many muscles other than the soleus, the H reﬂex of shortening will depend on the dispersion of the appears and continues to increase at stimulus inten- excitatory input and on the EPSP rise-time, both of sities well above 1 × MT provided that the reﬂex dis- which are greater in human subjects. Modiﬁed from Gracies, Pierrot-Deseilligny & Robain (1994), with permission. Difference between the full recruitment Conclusions of Ia afferents in cat and human experiments Whatever the mechanism responsible for the wide This difference (at 2 and 8 × Ia threshold, respec- range of electrical thresholds of Ia afferents, this tively) is probably due to the fact that in human factor needs to be taken into account for two rea- experiments afferents are stimulated through elec- sons. As a result, the thresh- tion may be underestimated in human experiments, old for a ﬁbre will be determined as much by its which are generally performed with much lower distance from the stimulating electrodes as by its stimulus intensities (≤1 × MT) in an attempt to acti- size. Organisation and pattern of connections 79 Katz, 1989), ﬂexor carpi radialis (FCR) and ﬂexor Organisation and pattern of carpiulnaris(FCU)(Malmgren&Pierrot-Deseilligny, connections 1988), deltoid, triceps brachii, extensor carpi radi- alis (ECR), ﬂexor digitorum superﬁcialis (FDS) and The efﬁcacy of a given Ia input in discharging a extensor digitorum (ED) (Gracies et al. It must be emphasised that these investiga- inhibition and the level of post-activation depres- tions were performed during weak voluntary con- sion at Ia terminals; (iii) any limitation produced by tractions(below5%MVC),andthemotorunitsstud- inhibitory circuits activated by the test volley, and ied were all in the low-threshold range. Differences in the efﬁcacy of homonymous Homonymous monosynaptic Ia excitation Ia excitation in ﬁring motoneurones Estimate of the efﬁcacy of the Ia input in ﬁring Evidence for homonymous Ia excitation in all homonymous motoneurones motoneurone pools This efﬁcacy may be assessed by the ease with which Hreﬂex the H reﬂex can be elicited at rest and by the size of At rest, H reﬂexes can be recorded from the the peak of excitation elicited in the PSTHs of sin- soleus, quadriceps and FCR in most healthy subjects gle motor units by stimulation subthreshold for the (Fig.
Most studies have been done with biso- These drugs improve cardiac function and decrease mortal- prolol discount prevacid 30mg online, carvedilol prevacid 15 mg without a prescription, or metoprolol; it is not yet known whether ity buy generic prevacid 30mg on line. They also relieve symptoms order prevacid 30 mg visa, increase exercise tolerance, some beta blockers are more effective than others. When one of and delay further impairment of myocardial function and pro- the drugs is used in clients with chronic HF, recommendations gression of HF (ie, ventricular remodeling). They act mainly to include starting with a low dose (because symptoms may initially decrease activation of the renin–angiotensin–aldosterone system, worsen in some clients), titrating the dose upward at approxi- a major pathophysiologic mechanism in HF. Significant the drugs prevent inactive angiotensin I from being converted to hemodynamic improvement usually requires 2 to 3 months of angiotensin II. Angiotensin II produces vasoconstriction and therapy, but effects are long lasting. Beneficial effects can be retention of sodium and water; inhibition of angiotensin II de- measured by increases in the left ventricular ejection fraction creases vasoconstriction and retention of sodium and water. Thiazides (eg, hydrochlorothiazide) can be used for An ACE inhibitor is usually given in combination with a di- mild diuresis in clients with normal renal function; loop diuretics uretic. All of the drugs have similar effects, but captopril, enalapril, (eg, furosemide) should be used in clients who need strong diuresis lisinopril, quinapril, and ramipril are FDA-approved for treatment or who have impaired renal function. Some clinicians use captopril initially because it has a short In acute HF, which is characterized by ﬂuid accumulation, a di- half-life and is rapidly eliminated when stopped, then switch to a uretic is the initial treatment. It acts to decrease plasma volume long-acting drug if captopril is tolerated by the client. Digoxin, a (extracellular ﬂuid volume) and increase excretion of sodium and beta-adrenergic blocking agent, or spironolactone may be added to water, thereby decreasing preload. With During ACE inhibitor therapy, clients usually need to see a moderate to severe HF (pulmonary edema), an IV loop diuretic is health care provider frequently for dosage titration and monitor- indicated. IV furosemide also has a vasodilatory effect that helps ing of serum creatinine and potassium levels for increases. Although diuretic therapy re- vated creatinine levels may indicate impaired renal function, in lieves symptoms, it does not improve left ventricular function and which case dosage needs to be reduced; elevated potassium lev- decrease mortality rates. Some clients may also need drugs to in- els indicate hyperkalemia, an adverse effect of the drugs. Angiotensin Receptor Blockers (ARBs) In chronic HF, an oral diuretic is a common component of treat- Losartan and other angiotensin receptor blockers (see Chap. Depending on the severity of symptoms or degree are similar to the ACE inhibitors in their effects on cardiac func- of HF, the regimen may also include an ACE inhibitor or ARB, a tion, although they are not FDA approved for treatment of HF. Valsartan recently received FDA approval for management Potassium-sparing diuretics (eg, amiloride, triamterene) are often of clients with HF who are unable to tolerate an ACE inhibitor given concurrently with potassium-losing diuretics (eg, thiazides (eg, development of a cough, a common adverse effect of ACE or loop diuretics) to help maintain normal serum potassium lev- inhibitors). Concomitant use of ACE inhibitors and nonsteroidal anti- Beta-Adrenergic Blocking Agents inflammatory drugs and the presence of diabetes mellitus increase Although beta blockers (see Chaps. The change evolved from a Both hypokalemia and hyperkalemia are cardiotoxic or impair better understanding of chronic HF (ie, that it involves more than heart function. Venous dilators pathophysiology of HF, results in increased interstitial ﬁbrosis that (eg, nitrates) decrease preload; arterial dilators (eg, hydralazine) may decrease systolic function and increase the risk of ventricular decrease afterload. Spironolactone is an aldosterone antagonist that re- combined to decrease both preload and afterload. The combina- duces the aldosterone-induced retention of sodium and water and tion has similar effects to those of an ACE inhibitor or an ARB, impaired vascular function. Although ACE inhibitors also decrease but may not be as well tolerated by clients. Spironolactone is given in Chapter 53; hydralazine and other vasodilators are discussed in a daily dose of 12. In clients with Oral vasodilators usually are used in clients with chronic HF adequate renal function (ie, serum creatinine 2. Overall, studies indicate that the at low doses, titrated to desired hemodynamic effects, and dis- addition of spironolactone improves cardiac function and reduces continued slowly to avoid rebound vasoconstriction. Vasodilators Vasodilators are essential components of treatment regimens for HF, and the beneﬁcial effects of ACE inhibitors and angiotensin Drugs at a Glance: Drugs for Heart Failure Routes and Dosage Ranges Generic/Trade Name Adults Children Inotropic Agents CARDIAC GLYCOSIDE Digoxin (Lanoxin) Digitalizing dose, PO 0. Maintenance dose, PO, IV, approximately 20–35% of the digitalizing dose Newborns: Digitalizing dose, PO 0. Maintenance dose, PO, IV, approximately 20–35% of the digitalizing dose.
Asdiscussedearlier buy prevacid 30 mg with mastercard,bin-to-binvariabilityinthecon- Normalisation of the results trol PSTH is commonly due to failure to maintain a steady background discharge rate buy prevacid 30 mg without prescription. Stimulation of afferents in the a peak (or a trough) in the PSTH and that of the median nerve at the wrist from intrinsic muscles of underlying PSP is complex (see p discount 30mg prevacid fast delivery. The calculations likethemodulationoftheon-goingEMG purchase 15 mg prevacid,PSTHscan involve measuring the latency of the monosynaptic beconstructedonlyforanactivemotoneuronepool. Ia peaks measured in PSTHs for the same unit after Some subjects ﬁnd it difﬁcult to maintain the dis- stimulation of homonymous Ia ﬁbres at two differ- chargeofaspeciﬁcmotorunitinisolation,andwhen ent sites (Chapter 2,p. Hook-wire by thetestvolleyortoensureachangeinpresynaptic electrodes allow selectivity and stability, but cannot inhibition of Ia terminals. The only important limi- be moved easily to record from different motor units tations are that it requires selective voluntary con- in a different site in the muscle. Itisalsoimpossibletodocumentthechangesin Afterhyperpolarisation transmission produced by voluntary effort. For this WhenIaorcorticospinalvolleysproduceaclearpeak reason the unitary H reﬂex described by Shindo et al. Weak lateeffectsmaythenbedemonstrated(i)bydecreas- ing the stimulus intensity (though this could reduce Unitary H reﬂex the size of the late effects), and (ii) by using the AHP to suppress the early peak. This would involve trig- Underlying principles and basic gering the stimulus earlier after the previous spike methodology so that the early peak falls within the AHP, but not so early that the late activity was also obscured (see Underlying principles p. By carefully controlling the stimulus it is possible to study the H reﬂex of single motor units. An in- Multiple peaks (or troughs) genious (but demanding) method has been described by Shindo et al. Thus, the double Recording peaks which occur in the PSTH at shorter intervals TheEMGpotentialofasinglemotorunitdischarging maybesafelyattributedtodoubleEPSPs,e. Conclusions Stimulation The PSTH is a powerful technique that allows single Theposteriortibialnerveisstimulatedtoproducean motoneurones to be investigated in human subjects Hreﬂex. The sizes of the test EPSPs (double-headed arrows in the top row of sketches in (b)–(d)) correspond to the CFS. Conditioning inhibition and facilitation are shown as increases and decreases in the CFS, respectively. Presence (●) and absence (❍)ofdischarge of the motor unit are shown in the bottom row. At rest, the test stimulus intensity is threshold indicates the weakest stimulus intensity determined automatically by computer. Repeated thataffectsthedischargeprobabilityofthevoluntar- automatic adjustments of the test stimuli make the ily activated motoneurone. The intensity that pro- ﬁring probability of the unit converge to 50% (FP50%) duces FP50% corresponds to the weakest stimulus (❍ and ● showing the absence and the presence of intensity that causes the motor unit to discharge ﬁring of the unit, respectively, in the bottom rows of with a 50% probability when at rest, and the differ- Fig. The stimulus intensity is increased ence between these intensities is the CFS, an indi- if the unit fails to discharge in response to the pre- rect measure of the size of the test Ia EPSP ne- ceding stimulus (❍ in C), and decreased if the unit cessary to make the motoneurone discharge when does discharge (● in D). When conditioning stimuli hyperpolarise or Stimulation of the motor cortex 39 depolarise the motoneurone, there are appropriate of PSTHs (to document the threshold for the Ia changes in the CFS (double-headed arrows in the EPSP)andthenduringtheexperimentalstudies. The CFS (ii) The method can be applied only in muscles in for a motor unit should therefore be a function of which an H reﬂex is recordable at rest. TherelationshipbetweentheCFS and the size of the test EPSP is approximately linear, Stimulation of the motor cortex andthesizeoftheCFScanbeusedasameasureofthe size of the average test Ia EPSP. When conditioning The development of techniques to stimulate the stimuli produce an IPSP, the resulting hyperpolar- motor cortex through the intact scalp and skull isation prevents the unit from ﬁring (❍ in Fig. A stronger stimulus intensity is then co-operative human subjects, and has led to new requiredtoproduceanEPSPsufﬁcientlylargeforthe diagnostic procedures and considerable advances motoneurone to ﬁre with a probability of 50%. Most of the pioneer versely,whenconditioningstimuliproducedepolar- work was undertaken by Marsden, Rothwell and col- isation, the sum of the conditioning and test EPSPs leagues, and this section is largely based on a com- causes the unit to ﬁre with a probability greater than prehensive review by Rothwell (1997). The technique was EMG responses evoked by validated by the demonstration that the sensitivity cortical stimulation tofemoral-inducedheteronymousIafacilitationwas the same for the unitary and the compound soleus Motor evoked potentials (MEPs) evoked by Hreﬂexes. The detection of cross-talk is Limitations particularlyimportantinthecontextofmotorcortex (i) A single motor unit must be held for a long time stimulation, because: (i) the stimulus is not focal; (ii) using a needle electrode – ﬁrst for a number even if it were, the response rarely involves a single 40 General methodology muscle; (iii) the effect observed following stimula- Methodology tion at a given site over the motor cortex depends on Anodal transcranial stimulation has a lower thresh- the existing level of background activity and can be old than cathodal stimulation (Rothwell et al. Merton and Morton nists to antagonists; (iv) reorganisation of the motor usedabipolarelectrodearrangement. Cross- of hand muscles, the anode was placed 7 cm lateral talk may be recognised by muscle palpation (except to the vertex and the cathode at the vertex; for acti- with near-threshold stimuli), and by the fact that the vation of the leg muscles, the anode was placed at frequencycontentofEMGactivitygeneratedatadis- the vertex and the cathode 6 cm anterior.
Despite this precocious devel- opment of beard and pubic hair buy prevacid 15mg online, he had never dropped his tes- ticles order prevacid 15mg free shipping. She then told me they had tried to have children for several years unsuccessfully after they married 30mg prevacid otc. Tey had even seen several doctors prevacid 15mg fast delivery, who told them his testicles were undescended and that was the cause of his infer- tility. One physician told them his testicles would have to be re- moved one day if they were to prevent cancer (there was a well- known increased risk of testicular cancer in undescended testicles). Despite these contacts with physicians, he had never had a sperm count. Apparently, her husband had been able to achieve full erection and penetration. Chromosome counts were just becoming available, so it was no surprise that he had not had what we would now call a complete workup earlier in his life. She told me he grew extremely rapidly before the ﬁrst grade and continued to grow until he was around nine years old, when he stopped completely. Her husband had often commented how he went from being the tallest and largest of his class in school in his early life to being one of the shortest in his teens. Te husband had developed male secondary sexual characteristics at a very early age—increase in facial hair, growth of his penis. Te wife had few questions and was relieved to know her hus- band was doing all right with the operation. Tere were open books on every surface and wooden slide boxes stacked in between the books, journals, and papers. He and I knew each other from some shared conferences at the medical school. I told him all I wanted to know was whether it was testicle, ovary, or a combination. I could hear myself breathing fast around the eyepieces and sensed the urgency to arrive at a decision both accurately and quickly. I then repeated my little lecture about the crucial need to hide everything we found. Te pathologist and I agreed to use generic Te Woman Who Believed She Was a Man 45 terms. We would avoid any terms that hinted of female or uterus, including the term hysterectomy, which was the operation I had recommended. Tese were the days of paternalism, and we thought nothing of withholding such informa- tion. Te surgeon, gynecolo- gist, and I huddled oﬀ to one side so none of the other team mem- bers would overhear us. I have always believed patients in operat- ing rooms can hear at some unconscious level, and this was one time I wanted to be sure the patient had no chance of overhearing anything at any level. I believed this patient had congenital adrenal hyperplasia, so-called virilizing adrenal hyperplasia; this meant simply that, before he was born, the adrenals made excessive male hormones (androgens). His fetal androgens, coming not from testicles but from the adrenals, caused the phallus (clitoris, in this case) to fuse with the urethra and form what appeared at birth to be a normal penis. Te child was born with what appeared to be undescended testicles; there was no rea- son to presume otherwise in that era. Te formation of the internal genitalia are not driven or af- fected by androgens but are directed by some signal from the chro- mosomes. Tus, they remained the normal female ovaries, fallo- pian tube, and uterus we saw in the abdomen. All of this embryology and endocrinology had just been worked out in detail in animals and was only now being applied to cases in humans. Tere was a beauty to the embryological story that had been discovered, so sequential and understandable. And like all hu- man systems, it could go awry—as it had in this patient.