Murali Pagala

Lifetime course of myasthenia gravis

Between 1940 and 2000 a total of 1976 patients with myasthenia gravis (MG) were studied. Diagnosis was made by improvement in weakness after anticholinesterase medication. The historical developments in diagnosis and treatment of MG are reviewed. We analyzed the clinical course of MG as influenced by age, gender, thymectomy, thymomectomy, and the presence of antibodies to acetylcholine receptors (AChR). The clinical course of MG was significantly influenced by age and gender, and these need special attention in managing patients. The most severe level of weakness and high mortality occurred during the first 1 to 2 years of the disease, after which many patients experienced improvement. For treating MG patients the usefulness of thymectomy remains to be proven, and novel drugs need to be developed to increase the number as well as normal functioning of the AChRs and other components of the neuromuscular system. Muscle Nerve, 2007

Rhabdomyolysis Related to Cocaine Abuse

Excerpt The rapid escalation in cocaine consumption in recent years has led to the recognition of new toxicities (1). Muscle necrosis caused by cocaine alone or with other factors has rarely been a...

AGING EFFECTS ON CONTRACTILITY OF LONGITUDINAL AND CIRCULAR DETRUSOR AND TRIGONE OF RAT BLADDER

PURPOSE Aging is associated with bladder dysfunction, including difficult voiding and urinary leakage. Voiding involves reduction in the bladder lumen in all dimensions brought about by contraction of the meshwork of longitudinal, circular and oblique layers of detrusor smooth muscles. Most in vitro physiological studies of the effects of aging on bladder function used the longitudinal detrusor. To understand the region specific effects of aging on bladder function the contractile responses of longitudinal and circular detrusor, and trigone segments of the bladder from young and old rats were monitored. MATERIALS AND METHODS These studies were performed using male Fisher 344 rats 6 months (young) and 27 months (old) old obtained through the National Institute on Aging. Each rat was anesthetized and the bladder was isolated. From each bladder a strip of longitudinal detrusor, circular detrusor and trigone was isolated and mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. Isometric contractions of the 3 bladder strips were monitored after electrical field stimulation, 120 mM. potassium and 1 to 1,000 microM. bethanechol using a digital oscilloscope. RESULTS In longitudinal detrusor from old rats there was no significant difference in the contractions evoked by electrical stimulation or high potassium but there was a significant reduction in contractions evoked by bethanechol compared with the responses of longitudinal detrusor from young rats. In circular detrusor from old rats there was a significant increase in contractions evoked by electrical stimulation and a slight increase in contractions produced by high potassium but no significant change in contractions evoked by bethanechol compared with the responses of circular detrusor from young rats. In trigone from old rats there was a significant decrease in contractions evoked by electrical stimulation, high potassium and bethanechol compared with young trigone. CONCLUSIONS The reduction in contractions evoked by bethanechol suggests an age related reduction in muscarinic receptors in the longitudinal detrusor of aged rats. An increase in contractions evoked by electrical stimulation without a change in contractions evoked by bethanechol suggests a decrease in compliance caused by an increase in collagen in the circular detrusor of aged rats. A general decline in all contractile responses, including those evoked by high potassium, suggests reduced membrane depolarization in the trigone of aged rats. The effect of aging is specific to different regions and functional components of the bladder, probably due to changes in muscarinic receptors, collagen and depolarization.

Giving toys to children reduces their anxiety about receiving premedication for surgery

Children have increased anxiety during the preoperative period. The administration of oral premedication to children is often met with apprehension, reluctance, or refusal. We sought to determine whether giving a small toy to the children would decrease the anxiety associated with taking oral premedication. This was a prospective study involving 100 children 3–6 yr of age randomized into two equal groups. The anxiety of each child was assessed using the Modified Yale Preoperative Anxiety Scale. The results showed significantly less anxiety in children who received a toy before oral administration of midazolam.

Association of super-super-obesity and male gender with elevated mortality in patients undergoing the duodenal switch procedure.

Background: Previous studies have reported that risk factors for elevated mortality after Roux-en-Y gastric bypass include male gender, as well as a very elevated BMI. The present study was aimed at determining whether these same risk factors applied to patients undergoing the duodenal switch (DS) operation. Materials and Methods: A retrospective chart review was performed of a cohort of 385 patients who underwent DS. The 30-day mortality of super-superobese (SSO) patients [BMI ≥60 kg/m2 (n=102)] was compared with the mortality of the super- and morbidly obese (SMO) patients [35<BMI<60 kg/m2 (n=283)]. Results: Overall mortality in SSO patients was 7.8% (8/102), compared with 0% (0/283) in SMO patients undergoing the same procedure (P<0.001). When a gender-based subgroup analysis was performed in the SSO patients, men had a 16.7% mortality (7/42) while women had only a 1.7% (1/60) mortality. Conclusions: In this study of patients undergoing DS, being SSO – specifically SSO men – was associated with increased mortality. Further studies will be needed to better determine the precise mechanism of these risk factors leading to such an elevation in mortality. Until then, caution should be exercised before performing DS in male patients with BMI ≥60 kg/m2.

FUNCTION OF M3 MUSCARINIC RECEPTORS IN THE RAT URINARY BLADDER FOLLOWING PARTIAL OUTLET OBSTRUCTION

PURPOSE Partial outlet obstruction of the rat urinary bladder leads to hypertrophy and alteration in contractility of the detrusor muscle involving changes in muscarinic receptors. m3 muscarinic receptor subtype has been known to play a predominant role in contractility of normal urinary bladder. The purpose of the present study was to assess the role of m3 receptors in contractility of the obstructed bladder. MATERIALS AND METHODS In male rats, partial outlet obstruction of the urinary bladder was performed by surgically tying a 6-0 suture around the bladder neck, reducing the diameter of it by 2/3 of the original size. Four weeks after the surgery, the bladders were removed and thin strips were microdissected. Similarly, bladder strips from age matched unoperated normal rats were obtained. Sets of four strips from four normal or four obstructed rats were mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. The tension responses evoked by optimal electrical field stimulation at 1, 10, 30, 50, and 100 Hz, and the contracture responses evoked by 120 mM potassium and 0.01 to 300.0 microM carbachol were recorded using a Nicolet digital oscilloscope. Similar responses were recorded in different sets of four strips following exposure to 10 and 100 nM 4-DAMP, which is a muscarinic antagonist with a high affinity for m3 and m1 receptor subtypes. RESULTS The obstructed bladders showed 119% increase in weight. In control physiological solution, the obstructed bladder strips did not show significant difference in electrically-evoked tension or carbachol contractures, but showed significantly lower potassium contractures compared with normal bladder strips. 4-DAMP at 10 to 100 nM significantly reduced the electrically evoked tension responses by about the same degree in normal and obstructed bladders, without affecting the potassium contractures. It significantly increased the EC50 values for carbachol contractures in normal bladder, and to a significantly lesser extent in obstructed bladder. Schild plots using the Hill transformed EC50 values showed that the pA2 value for 4-DAMP was not significantly different in normal and obstructed bladders. CONCLUSIONS Significantly smaller potassium contracture in the obstructed bladder indicates that depolarizability of the detrusor muscle membrane, and consequently the activity of voltage-gated Ca2+ channels may be reduced in the detrusor after partial outlet obstruction. Lack of a significant difference in the effect of 4-DAMP on the electrically evoked tension responses and in the pA2 values for 4-DAMP assessed by carbachol contractures, in normal and obstructed bladder strips, indicates that m3 muscarinic receptors still play a predominant role in causing detrusor contractility in the obstructed bladder, as in the normal bladder.

Skeletal muscle fatigue and physical endurance of young and old mice

In order to evaluate the role played by muscular and extramuscular factors in the development of fatigue in old age, the time course of fatigue in isolated skeletal muscles and spontaneous motor activity and endurance of whole animals were monitored using young (3–6 months) and old (34–36 months) CF57BL/6J mice. The isolated extensor digitorum longus (EDL) and soleus muscles from old mice had smaller (P < 0.05) mass and developed lower (P < 0.02) maximal tetanic tension at 100‐Hz stimulation than the muscles of young mice. During stimulation at 30 Hz every 2.5 s, a 50% decline in original tetanic tension occurred by 109 s in young EDL and 129 s in old EDL, but by 482 s in young soleus and 1134 s (projected) in old soleus, indicating more (P < 0.05) resistance to fatigue in old than young soleus. However, the old mice showed significantly fewer (P < 0.002) spontaneous ambulatory movements than the young mice. On a treadmill with a belt speed of 10 m/min at an inclination of 0°, the old mice could only run for 22 min compared to 39 min ran by young mice (P < 0.02). They took more rest periods (P < 0.02) than the young mice. In a quantitative swimming monitor, the old mice swam for a shorter (P < 0.05) time than young mice (20.4 min compared to 28.6 min). Integrated swimming activity at 20 min was smaller (P < 0.05) in old mice than in young mice (413 g/s compared to 628 g/s). Hence increased fatigue in old age is not caused by impairment of processes within the muscles, but by impairment of central or extramuscular processes.

Systemic absorption of oral vancomycin in patients with Clostridium difficile infection

Abstract Oral vancomycin is utilized in the treatment of severe Clostridium difficile infection (CDI). We prospectively measured serum vancomycin concentrations (SVC) in patients treated with oral vancomycin. The SVC was measured by immunoassay prior to, and at least 3 days after, the administration of oral vancomycin 125 mg every 6 h. Patients treated with intravenous vancomycin were excluded. Fifty-seven patients with a mean age of 74 y (± 18) were enrolled. There was no detectable SVC in 56 patients (98%); 1 patient had a transient SVC of 6.7 μg/ml that was not detectable on subsequent testing. The severity of the CDI and/or renal failure did not have an effect on SVC. Orally administered vancomycin at 125 mg 4 times daily was not absorbed from the gastrointestinal tract.

Gender is an essential determinant of blood transfusion in patients undergoing coronary artery bypass graft procedure

STUDY OBJECTIVE To determine factors that account for gender difference in the need for blood transfusion in coronary artery bypass graft (CABG) patients. DESIGN Retrospective study of consecutive patients. SETTING Anesthesiology department of a teaching hospital. PATIENTS 253 CABG patients (163 males and 90 females). INTERVENTIONS Packed red blood cells (PRBCs), platelets, and fresh frozen plasma (FFP) were transfused depending on the need of each patient. MEASUREMENTS AND MAIN RESULTS For each patient, we recorded the gender, age, weight, height, body surface area (BSA), and duration of surgery. Hematocrit (Hct) levels prior to surgery, end of surgery, and at discharge from the hospital were recorded. PRBC administration and use of FFP and platelets were noted. Differences between the data for female and male patients were evaluated using Students t-test, Chi-square test, and regression analysis. Approximately 60% female and only 20% male patients received PRBCs intraoperatively, whereas 78% females and only 43% males received PRBCs during their entire hospital stay. On average, females received 1.20 units of PRBCs intraoperatively and 2.38 units during the entire hospital stay, while the males received 0.31 units and 1.36 units for similar periods. Gender differences in PRBC transfusion persisted even when females and males were compared within the same subgroups for age, weight, duration of surgery, and preoperative Hct. PRBC units given intraoperatively had a significant correlation with age and preoperative Hct in females, but they had a significant correlation with age, preoperative Hct, and duration of surgery in males. PRBCs given during the entire hospital stay, however, had significant correlation with age, preoperative Hct, and duration of surgery in both females and males. Multiple logistic regression analysis showed that the probability of a patient receiving or not receiving PRBC transfusion is significantly influenced by age, preoperative PRBC mass, duration of surgery, and gender. CONCLUSION Gender is an independent essential determinant of blood transfusion in CABG patients, and it may interact with age, weight, preoperative Hct, duration of surgery, and other factors in determining the probability of transfusion.

Immediate clinical outcomes in preterm neonates receiving antenatal magnesium for neuroprotection

Abstract Background: Antenatal magnesium sulfate can potentially reduce the risk of cerebral palsy in neonates delivered between 24 and 32 weeks of gestational age. Some studies using high-dose magnesium sulfate for neuroprotection have reported increased perinatal mortality. Methods: A retrospective study was conducted on 475 neonates born between 24 and 32 weeks of gestational age. Serum magnesium level in the first 24 h of life was used to stratify the neonates treated with antenatal magnesium into four subgroups: A (<2.5 mEq/L), B (≥2.5 to <3.5 mEq/L), C (≥3.5 to <4.5 mEq/L), and D (≥4.5 mEq/L). Primary outcome of survival without intraventricular hemorrhage (IVH) and/or periventricular leukomalacia (PVL) along with secondary outcomes, such as Apgar scores, resuscitation, intubation, broncho-pulmonary dysplasia, retinopathy of prematurity (ROP), patent ductus arteriosus (PDA), time to reach full feeds, length of stay (LOS), and mortality during immediate neonatal period were studied. Results: Of the 475 neonates included in the study, 289 (61%) received antenatal magnesium sulfate. Primary outcome of survival without IVH and/or PVL among the preterm neonates was 70.9% in those receiving and 74.2% in those not receiving antenatal magnesium (P=0.25). There were higher incidences of ROP (P=0.02), PDA (P=0.01), greater time to reach full feeds (P=0.03), and increased LOS (P=0.01) in neonates who had received antenatal magnesium. These findings were not statistically significant when the data were corrected for gestational age and birth weight. Among the subgroups, there was a significantly increased mortality rate (P<0.05) with increasing magnesium levels (5% vs. 16.9%, P<0.05 in groups A vs. D) and a trend toward higher intubation rate (P=0.1) and PDA (P=0.14). Conclusion: Antenatal magnesium is safe in the immediate postnatal period; however, in the subset of preterm neonates with serum magnesium levels >4.5 mEq/L, there is increased mortality independent of birth weight and gestational age. Identification of these neonates and appropriate dosing for their antenatal neuroprotection needs to be studied.