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Biomedical subjects

N Rawal

Publications and source records attributed to N Rawal.

At least 37 records · Page 2Linked to original sources
PubMed2003

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↗
PubMed2002

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↗
PubMed2001

[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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

The analgesic efficacy of patient-controlled ropivacaine instillation after Cesarean delivery.

To assess the efficacy and safety of wound instillation of ropivacaine, when administered via a patient-controlled elastometric pump, 50 term parturients undergoing cesarean delivery were enrolled into this prospective, placebo-controlled, double-blinded study. In all cases, a standard spinal anesthetic was administered. After the surgery, a multihole 20-gauge epidural catheter (B. Braun, Melsungen, Germany) was placed above the fascia such that the tip was sited at the point that demarcated 50% of the length of the surgical wound. Thereafter, the catheter was connected to the elastometric pump. According to a computer-generated randomization schedule, the pump was filled with either ropivacaine 0.2% (Ropivacaine Group) or an equal volume of sterile water (Control Group). Postoperatively, patient-controlled analgesia was administered via the elastometric pump. During the first 6 postoperative hours, a coinvestigator administered "rescue" morphine (2 mg, IV). Thereafter, "rescue" dipyrone (1 g) was administered on patient request. In a subset of 10 patients, blood ropivacaine levels were assessed. Compared with the Control Group, significantly fewer patients in the Ropivacaine Group received "rescue" morphine (92% vs. 48%, respectively) (P<0.01). The total "rescue" morphine administered during the first 6 postoperative hours was 2+/-3 mg vs. 10+/-5 mg (P<0.01) for the Ropivacaine and Control Groups, respectively. Patient-generated resting pain scores were similar between the groups. However, pain scores generated after coughing and leg raise were significantly (P<0.04) less in the Ropivacaine Group. More patients in the Ropivacaine Group than in the Control Group described their analgesia as good or excellent. In the subset of patients (n = 10) studied, unbound ropivacaine blood levels were below the toxic threshold (600 ng/mL). However, blood ropivacaine accumulation was noted. All patients stated that the elastometric pump was easy to use. Ropivacaine wound instillation via an elastometric pump is a simple technique that provides safe and effective analgesia after cesarean delivery.

Adult↗
PubMed2000

Combined regional and general anaesthesia.

Combining regional and general anaesthesia can have many advantages, particularly in patients undergoing major thoracic, abdominal or orthopaedic surgery. The use of regional anaesthetic techniques in anaesthetized children is an accepted standard of care, because needle and procedure phobias are very common and can result in severe anxiety, an inability to cooperate and sudden unpredictable movement. Epidural local anaesthetics have the potential of attenuating sympathetic hyperactivity, maintaining bowel peristalsis, sparing the use of opioids, and facilitating postoperative feeding and out-of-bed activity. Catheter techniques allow excellent and prolonged postoperative analgesia using epidural or peripheral nerve blocks. However, the superiority of regional techniques for hip fracture surgery and carotid endarterectomy has been disputed in several recent studies. As part of the combination technique, epidural block may in fact decrease blood flow in free flap surgery by a steal phenomenon, and increase intrapulmonary shunting during one-lung ventilation. The present review focuses on the use of a combination of regional and general anaesthesia for a variety of surgical procedures. It also compares the two anaesthetic techniques in elderly patients. The review is based on studies published during the past year.

Journal Article↗
PubMed1999

Inhibition of complement by covalent attachment of rosmarinic acid to activated C3b.

Rosmarinic acid has been reported to inhibit complement activation in vivo as well as in vitro. Previous studies suggested that the inhibitory effect was due to inhibition of C3/C5 convertases, but inhibition of C3b attachment would yield the same results. Recent work in our laboratory demonstrated that compounds with polyhydroxylated phenyl rings are highly reactive with the thioester bond in nascent C3b. These compounds block complement activation by preventing attachment of C3b to the activating surface. Because rosmarinic acid contains two 3,4-dihydroxyphenyl groups, the current study was undertaken to re-examine the mechanism of inhibition by analyzing the effect of rosmarinic acid on C3b attachment. In assays using purified complement proteins, rosmarinic acid inhibited covalent attachment of C3b to cells with an 1C50 = 34 microM. Inhibition of C5 convertase activity required 1500 microM rosmarinic acid, and no significant inhibition of the C3 convertase enzyme, which produces C3b from C3, was observed at 10,000 microM. In hemolytic assays using human serum, rosmarinic acid was shown to inhibit activation of both the classical (IC50 = 180 microM) and the alternative (IC50 = 160 microM) pathways of complement. Rosmarinic acid concentrations up to 10,000 microM did not cause direct inactivation of C3. Radioiodination of rosmarinic acid was used to demonstrate covalent activation-dependent incorporation of rosmarinic acid specifically into the thioester-containing alpha'-chain of nascent C3b. These findings indicate that inhibition of complement activation by rosmarinic acid is due to the reaction of rosmarinic acid with the activated thioester of metastable C3b, resulting in covalent attachment of the inhibitor to the protein.

Animals↗
PubMed1999

Epidural and spinal agents for postoperative analgesia.

The discovery of opioid receptors and the subsequent development of the technique of epidural and intrathecal opioid administration are undoubtedly two of the most significant advances in pain management in recent decades. The use of spinal opioids is widespread and increasing. The technique is used widely to treat intraoperative, postoperative, traumatic, obstetric, chronic, and cancer pain. Newer developments include the increasing use of combined local anesthetics and opioids or nonopioids and also PCEA, particularly in the obstetric population. Meta-analysis of controlled trials has demonstrated improved pulmonary outcome in patients receiving epidural postoperative analgesia. Although rare, respiratory depression continues to be a major problem of the technique. None of the currently available opioids is completely safe; however, extensive international experience has shown that patients receiving spinal opioids for postoperative analgesia can be safely nursed on regular wards, provided that trained personnel and appropriate guidelines are available. The importance of a good acute pain service to provide the safe and effective use of spinal opioids cannot be overemphasized.

Analgesia, Epidural↗