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Biomedical subjects

N Rawal

Publications and source records attributed to N Rawal.

At least 19 recordsLinked to original sources

New parkin mutations and atypical phenotypes in families with autosomal recessive parkinsonism.

The frequency of parkin mutations was evaluated in 30 families of highly diverse geographic origin with early-onset autosomal recessive parkinsonism. Twelve different mutations, six of which were new, were found in 10 families from Europe and Brazil. Patients with parkin mutations had significantly longer disease duration than patients without the mutation but with similar severity of disease, suggesting a slower disease course. Two patients with parkin mutations had atypical clinical presentation at onset, with predominant tremor when standing.

Adult↗

Analgesia following music and therapeutic suggestions in the PACU in ambulatory surgery; a randomized controlled trial.

BACKGROUND: This study was designed to determine whether music (M), or music in combination with therapeutic suggestions (M/TS) could improve the postoperative recovery in the immediate postoperative in daycare surgery. METHODS: One-hundred and eighty-two unpremedicated patients who underwent varicose vein or open inguinal hernia repair surgery under general anaesthesia were randomly assigned to (a). listening to music (b). music in combination with therapeutic suggestions or (c). blank tape in the immediate postoperative period. The surgical technique, anaesthesia and postoperative analgesia were standardized. Analgesia, the total requirement of morphine, nausea, fatigue, well-being, anxiety, headache, urinary problems, heart rate and oxygen saturation were studied as outcome variables. RESULTS: Pain intensity (VAS) was significantly lower (P = 0.002) in the M (2.1), and the M/TS (1.9) group compared with the control group (2.9) and a higher oxygen saturation in M (99.2%) and M/TS (99.2%) group compared with the control (98.0%), P < 0.001, were found. No differences were noted in the other outcome variables. CONCLUSION: This controlled study has demonstrated that music with or without therapeutic suggestions in the early postoperative period has a beneficial effect on patients' experience of analgesia. Although statistically significant, the improvement in analgesia is modest in this group of patients with low overall pain levels.

Ambulatory Surgical Procedures↗

Patient-controlled regional analgesia (PCRA) with ropivacaine after arthroscopic subacromial decompression.

BACKGROUND: The aim of the study was to evaluate postoperative analgesia and safety of wound instillation of ropivacaine either by a single dose or a patient-controlled regional anaesthesia (PCRA) technique. METHODS: In 40 patients undergoing arthroscopic subacromial decompression the surgeon placed a catheter into the subacromial space at the end of the operation. In Phase I (10 patients), ropivacaine 250 mg was injected twice within 1 h. In Phase II, 30 patients were randomised into three groups: group prilocaine-ropivacaine (PR) = 20 ml of 1% prilocaine-epinephrine injected preoperatively into the subacromial bursa + 20 ml of 0.5% ropivacaine infused in the catheter postoperatively; group saline-ropivacaine (SR) = saline-epinephrine (20 ml) preoperatively + 0.5% ropivacaine as in group PR; group saline-saline (SS) = saline-epinephrine (20 ml) preoperatively + saline postoperatively. The PCRA pump was filled with local anaesthetic or saline to allow boluses of 10-ml each, maximum one bolus/h, via the catheter. Pain relief, side-effects and venous plasma concentration of ropivacaine were evaluated during a 24-h-test period. RESULTS: The free plasma concentration of ropivacaine was 0.12 + 0.041 mg l-1 in Phase I. No adverse effects were seen. In Phase II pain at rest and on movement was lower in group PR than in group SS during the first 30 min postoperatively (P < 0.05). Group PR had the lowest morphine consumption (P < 0.05). Five to seven boluses were administered via the PCRA-pump, and 20 min after administration of the study solution, pain was lower in groups PR and SR compared with group SS (P < 0.001). CONCLUSIONS: Preoperative intrabursal prilocaine with epinephrine + postoperative subacromial administration of ropivacaine by PCRA-technique provided the most effective analgesia with no major side-effects. The free plasma concentrations of ropivacaine were far below toxic concentrations.

Adult↗

A comparison of intra-operative or postoperative exposure to music--a controlled trial of the effects on postoperative pain.

The effect of intra-operative compared to postoperative music on postoperative pain was evaluated in a controlled trial. In all, 151 patients undergoing day case surgery for inguinal hernia repair or varicose vein surgery under general anaesthesia were randomly allocated to three groups: group 1 listened to music intra-operatively, group 2 listened to music postoperatively and group 3, the control group, listened to 'white noise'. The anaesthetic and postoperative analgesic techniques were standardised. Pain was assessed using a numeric rating scale (0-10) and patients requirements for postoperative morphine, paracetamol and ibuprofen was recorded. The effect of music on nausea, fatigue and anxiety was also investigated. The results showed that patients exposed to music intra-operatively or postoperatively reported significantly lower pain intensity at 1 and 2 h postoperatively and patients in the postoperative music group required less morphine at 1 h compared to the control group. No differences were noted in the other variables. This study demonstrates that there is a short-term pain-reducing effect of music therapy however, the beneficial effects do not differ if the patient is exposed to music intra-operatively or postoperatively.

Adult↗

Cytological and histological outcome following a borderline cervical smear.

A prospective cytological and histological study was conducted in 627 women with borderline nuclear abnormality to assess its clinical significance in an attempt to reach a sound policy of management. The incidence of dyskaryosis was 10.9% at a 6-month repeat smear after the first borderline smear. The detection of cervical intraepithelial neoplasia (CIN) after two borderline smears increased to 21.15% on cytology and 40.75% on histology. Additionally, there were two cases of glandular intraepithelial neoplasia and one case of adenocarcinoma detected on histology after having borderline nuclear changes reported on cytology; 39.7% of these women with initial borderline cervical smear were under the age of 30 years. The high prevalence of borderline nuclear abnormality in younger women and a poor correlation between these abnormalities and severity of CIN suggest that repeat cytology is a less than optimal management for these women.

Adenocarcinoma↗

Structure and function of complement C5 convertase enzymes.

The multisubunit enzymes of the complement system that cleave C5 have many unusual properties, the most striking of which is that they acquire their specificity for C5 following cleavage of another substrate C3. C5 convertases are assemblies of two proteins C4b and C2a (classical or lectin pathways) or C3b and Bb (alternative pathway) and additional C3b molecules. The catalytic complexes (C4b, C2a or C3b, Bb) are intrinsically unstable ( t (1/2)=1-3 min) and the enzymes are controlled by numerous regulatory proteins that accelerate this natural decay rate. Immediately after assembly, the bi-molecular enzymes preferentially cleave the protein C3 and exhibit poor activity toward C5 (a K (m) of approx. 25 microM and a C5 cleavage rate of 0.3-1 C5/min at V (max)). Efficient C3 activation results in the covalent attachment of C3b to the cell surface and to the enzyme itself, resulting in formation of C3b-C3b and C4b-C3b complexes. Our studies have shown that deposition of C3b alters the specificity of the enzymes of both pathways by changing the K (m) for C5 more than 1000-fold from far above the physiological C5 concentration to far below it. Thus, after processing sufficient C3 at the surface of a microorganism, the enzymes switch to processing C5, which initiates the formation of the cytolytic membrane attack complex of complement.

Animals↗

[Postoperative pain an unnecessary suffering. A model of "emergency pain relief" implemented in Orebro].

Despite unprecedented interest in the understanding of pain mechanisms and pain management, a significant number of patients continue to experience unacceptable pain after surgery. An acute pain service (APS) has to include regular pain assessment and documentation, "make pain visible", and bedside teaching of nurses in order to provide safe and cost-effective analgesia. The acute pain team in Orebro includes anaesthesiologists, surgeons, specialist acute pain nurses as well as ward nurses. A combination of less invasive surgery, effective analgesia and strategies for rehabilitation can reduce post-operative morbidity and shorten hospitalization.

Acute Disease↗

Formation of high-affinity C5 convertases of the alternative pathway of complement.

Cleavage of C5 by C5 convertase is the last enzymatic step in the complement activation cascade leading to the formation of the cytolytic proteolytically activated form of C5 (C5b)-9 complex. In the present study, we examined the effect of the density of C3b (the proteolytically activated form of C3) on the function of the noncatalytic subunit of natural surface-bound forms of the enzyme. A comparison of the kinetic parameters of C5 convertases assembled on three surfaces (zymosan, rabbit erythrocytes, and sheep erythrocytes) were similar and revealed that the average K:(m) decreased approximately 28-fold (5.2-0.18 microM) when the density of C3b was increased from approximately 18,000 to 400,000 C3b/cell. Very-high-affinity C5 convertases were generated when preformed C3 convertases were allowed to self amplify by giving them excess C3. These convertases exhibited K(m) from 0.016 to 0.074 microM, well below the normal plasma concentration of C5 in blood (0.37 microM). The results suggest that in serum convertases formed with monomeric C3b will be relatively inefficient in capturing C5 but will continue to cleave C3 opsonizing the cell surface for phagocytosis, whereas convertases formed with C3b-C3b complexes in areas of high C3b density will primarily cleave C5. The catalytic rate of these convertases approaches maximum velocity, thereby switching the enzyme from cleavage of C3 to cleavage of C5, and production of the cytolytic C5b-9 complex.

Animals↗

Postoperative recovery following outpatient pediatric myringotomy: a comparison between sevoflurane and halothane.

STUDY OBJECTIVE: To assess recovery in children undergoing myringotomy and anesthetized using sevoflurane or halothane with special reference to the phenomenon of excitation reported in previous studies. DESIGN: Prospective, randomized, single-blind study. SETTING: Regional (district general) hospital. PATIENTS: 60 healthy, physical status I children (aged 3 to 8 years) presenting for elective outpatient myringotomy. INTERVENTIONS: The children were premedicated with midazolam and paracetamol and randomly allocated to one of two groups: Group H were induced with halothane (0.5% to 5%) and Group S with sevoflurane (1% to 8%). Anesthesia was maintained with oxygen (FIO(2) = 0.33), nitrous oxide, and the study drug. No opioids were administered during surgery. Postoperatively, propofol was given (1 mg/kg) if the child was crying and uncontrollable on the excitation scale for >5 minutes. Total analgesic consumption and side effects were recorded. MEASUREMENTS AND MAIN RESULTS: Postoperatively, the following parameters were recorded: time to eye opening, excitation, pain, time to sit unaided, time to drink water, time to walk, and time to discharge home. No differences were found in the demographic data, duration of anesthesia and operation, time to loss of eyelash reflex, time to waking up, incidence of postoperative excitation (7% and 8% in the sevoflurane and halothane groups respectively), pain, or postoperative nausea and vomiting. The ability to sit and walk, and the time to discharge home (mean 60.4 min vs. 67.1 min, respectively) was similar between the groups. CONCLUSIONS: Although some studies have reported a high incidence of excitation following sevoflurane anaesthesia, we found no differences between halothane and sevoflurane. This finding could be due to the midazolam given as premedication as well as minimal postoperative pain in these children.

Akathisia, Drug-Induced↗

Structure/function of C5 convertases of complement.

C5 convertases are serine proteases that cleave both C3 and C5. Alternative pathway C3/C5 convertases formed with monomeric C3b (C3b,Bb) because of their weak interaction with C5 primarily cleave C3 thereby opsonizing the cell surface with C3b. In contrast, C3/C5 convertases formed with a high density of C3b/cell exhibit higher affinities for C5 as indicated by Km values well below the physiological concentration of C5 in blood. These C3/C5 convertases bind C5 efficiently and cleave it at a velocity approaching Vmax thereby switching the enzyme from C3 cleavage to production of the cytolytic C5b-9 complex. Studies of the structure of C3/C5 convertases have postulated that C4b-C3b and C3b-C3b dimers from high affinity C5 binding sites while indel studies have shown two binding sites in C5 for the convertase in addition to the C5 cleavage site. Together, these studies indicate that with increasing deposition of C3b on the surface, C3b complexes are formed which through multivalent attachment bind the substrate C5 with higher affinities, thereby converting the low affinity C3/C5 convertases to high affinity C5 convertases. The process underlying the formation of high affinity C5 convertases during complement activation is discussed.

Animals↗

Improved recovery after music and therapeutic suggestions during general anaesthesia: a double-blind randomised controlled trial.

PURPOSE: This study was designed to determine whether music or music in combination with therapeutic suggestions in the intra-operative period under general anaesthesia could improve the recovery of hysterectomy patients. METHODS: In a double-blind randomised clinical investigation, 90 patients who underwent hysterectomy under general anaesthesia were intra-operatively exposed to music, music in combination with therapeutic suggestion or operation room sounds. The anaesthesia was standardised. Postoperative analgesia was provided by a patient-controlled analgesia (PCA). The pain scores were recorded by means of a visual analogue scale. Nausea, emesis, bowel function, fatigue, well-being and duration of hospital stay were studied as outcome variables. RESULTS: On the day of surgery, patients exposed to music in combination with therapeutic suggestions required less rescue analgesic compared with the controls. Patients in the music group experienced more effective analgesia the first day after surgery and could be mobilised earlier after the operation. At discharge from the hospital patients in the music and music combined with therapeutic suggestion group were less fatigued compared to the controls. No differences were noted in nausea, emesis, bowel function, well-being or length of hospital stay between the groups. CONCLUSION: This double-blind study has demonstrated that intra-operative music and music in combination with therapeutic suggestions may have some beneficial effects on postoperative recovery after hysterectomy. Further controlled studies are necessary to confirm our results.

Analgesics, Opioid↗

Postoperative analgesia at home after ambulatory hand surgery: a controlled comparison of tramadol, metamizol, and paracetamol.

We compared in a prospective, randomized, double-blinded study the analgesic efficacy of three drugs in 120 ASA I and II patients scheduled to undergo ambulatory hand surgery with IV regional anesthesia. At discharge, oral analgesic tablets were prescribed as follows: tramadol 100 mg every 6 h, metamizol 1 g every 6 h, and paracetamol (acetaminophen) 1 g every 6 h. Rescue medication consisted of oral dextropropoxyphene 100 mg on demand. Analgesic efficacy was evaluated by self-assessment of pain intensity by visual analog score at six different time intervals during the 48-h study period. Patients also recorded global pain relief on a 5-grade scale, total number of study and rescue analgesic tablets, frequency and severity of adverse effects, sleep pattern, and overall satisfaction. None of the study drugs alone provided effective analgesia in all patients. The percentage of patients who required supplementary analgesics was 23% with tramadol, 31% with metamizol, and 42% with acetaminophen. Tramadol was the most effective analgesic, as evidenced by low pain scores, least rescue medication, and fewest number of patients with sleep disturbance. However, the incidence of side effects was also increased with tramadol. Seven patients (17.5%) withdrew from the study because of the severity of nausea and dizziness associated with the use of tramadol. Metamizol and acetaminophen provided good analgesia in about 70% and 60% of patients, respectively, with a decreased incidence of side effects. Despite receiving oral analgesic medication, up to 40% of patients undergoing hand surgery experienced inadequate analgesia in this controlled trial. Although tramadol was more effective, its use was associated with the highest frequency and intensity of adverse effects and the most patient dissatisfaction. Metamizol and acetaminophen provided good analgesia with a small incidence of side effects. For patients undergoing ambulatory hand surgery, postoperative pain can last longer than 2-3 days, and there is a need for both better education before the procedure and oral analgesic therapy at home.

Acetaminophen↗

Treating postoperative pain improves outcome.

Recent surveys show that many patients still receive inadequate post-surgical analgesia, this problem is international in character. Analgesia techniques like patient-controlled analgesia (PCA) and spinal opioids alone or in combination with local anaesthetics provide superior pain relief compared to intermittent i.m. injections of opioids. Patient satisfaction with these techniques is high; however, reduced pain and suffering or high patient satisfaction is not considered sufficient in this age of diminished health care budgets. There is no overwhelming evidence that effective postoperative pain relief assures good postoperative outcome. Most studies lack sufficient statistical power to detect clinically significant differences. A meta-analysis showed higher patient satisfaction with i.v. PCA compared to i.m. opioid injection. Although PCA still is the standard of care there's little rational or scientific evidence that i.v. PCA improves outcome. A meta-analysis of randomized, controlled trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after various procedures has shown that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity. None of the other analgesic techniques had a significant impact on pulmonary outcome. There are few outcome studies with peripheral nerve blocks. Evidence that peripheral nerve blocks are better than PCA and safer than epidural increases. One reason why improved outcome is difficult to demonstrate is that pain management strategies are not integrated with overall perioperative care and postoperative rehabilitation of the patient. The importance of a good APS in developing cost-effective, evidence-based pain treatment strategies for different surgical procedures should not be underestimated.

Analgesia↗

Functional role of the noncatalytic subunit of complement C5 convertase.

The C5 convertase is a serine protease that consists of two subunits: a catalytic subunit which is bound in a Mg2+-dependent complex to a noncatalytic subunit. To understand the functional role of the noncatalytic subunit, we have determined the C5-cleaving properties of the cobra venom factor-dependent C5 convertase (CVF, Bb) made with CVF purified from the venom of Naja naja (CVFn) and Naja haje (CVFh) and compared them to those for two C3b-dependent C5 convertases (ZymC3b,Bb and C3b,Bb). A comparison of the kinetic parameters indicated that although the four C5 convertases (CVFn,Bb, ZymC3b,Bb, CVFh,Bb, and C3b,Bb) had similar catalytic rate constants (kcat = 0.004-0.012 s-1) they differed 700-fold in their affinity for the substrate as indicated by the Km values (CVFn,Bb = 0.036 microM, ZymC3b,Bb = 1.24 microM, CVFh,Bb = 14.0 microM, and C3b,Bb = 24 microM). Analysis of binding interactions between C5 and the noncatalytic subunits (CVFh or C3b, or CVFn) using the BIAcore, revealed dissociation binding constants (Kd) that were similar to the Km values of the respective enzymes. The kinetic and binding data demonstrate that the binding site for C5 resides in the noncatalytic subunit of the enzyme, the affinity for the substrate is solely determined by the noncatalytic subunit and the catalytic efficiency of the enzyme appears not to be influenced by the nature of this subunit.

Animals↗

The combined spinal-epidural technique.

Epidural and spinal blocks are well-accepted regional techniques, but they have several disadvantages. The CSE technique can reduce or eliminate the risks of these disadvantages. CSE block combines the rapidity, density, and reliability of the subarachnoid block with the flexibility of continuous epidural block to extend duration of analgesia. The CSE technique is used routinely at many institutions, particularly for major orthopedic surgery and in obstetrics. It has been used in tens of thousands of patients without any reports of major problems. Although at first sight the CSE technique appears to be more complicated than epidural or spinal block alone, intrathecal drug administration and siting of the epidural catheter are both enhanced by the combined, single-space, needle-through-needle method. Concerns about the epidural catheter entering the theca via the small puncture hole are now considered to be unfounded, but as with all epidural catheter techniques, vigilant monitoring of the patient during and after any injection is paramount. CSE is an effective way to reduce the total drug dosage required for anesthesia or analgesia. The intrathecal injection achieves rapid onset with minimal doses of local anesthetics and opioids, and the block can be prolonged with low-dose epidural maintenance administration. In addition, the sequential CSE method can be used to extend the dermatomal block with minimal additional drugs or even saline. Reduction in total drug dosage has made truly selective blockade possible. Many studies have confirmed that low-dose CSE with local anesthetic and opioid, or low-dose epidural block alone, will provide effective analgesia with minimal motor and proprioceptive block. Such neurologic selective blockade has made it possible for most patients to walk and bear down normally in labor or postoperatively. There remains concern about the risk of infection being increased when the CSE technique is used in place of epidural block alone. Despite a recent flurry of reports of meningitis with CSE procedures, there is no evidence the CSE block is more hazardous than epidural or subarachnoid block alone. Arguably, the single-space, needle-through-needle CSE technique will continue to improve with new needle designs and other advances to improve further the success rate and reduce complications, such as neurotrauma, PDPH, and infection. Over the past decade it has become clear that the CSE technique is a significant advance in regional blockade.

Analgesia, Epidural↗