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Biomedical subjects

N Rawal

Publications and source records attributed to N Rawal.

At least 73 records · Page 4Linked to original sources
PubMed1995

Risk of catheter migration during combined spinal epidural block: percutaneous epiduroscopy study.

Combined spinal epidural (CSE) block with the needle-through-needle technique has become increasingly popular during recent years. However, the risk of epidural catheter penetrating dura mater through the hole made by the spinal needle (migration) is a major concern. In 15 fresh cadavers a percutaneous epiduroscopy technique with a rigid epiduroscope and video recording was used to assess the risk of catheter migration when a CSE block is performed. The experimental sequence included (a) one dural hole made by the spinal needle, (b) multiple (five) dural holes made by the spinal needle, and (c) a dural hole made by Tuohy needle. Twenty-four experimental sequences were performed in the lumbar region. Four sequences were failures due to technical problems. In the remaining 20 cases, the anatomic structures in the epidural space were recognized easily. The epidural space appears to be only a potential space, kept open either by epiduroscope or by repeated injections of air or saline. The dural holes made by Tuohy and spinal needles, and the ease of difficulty of catheter penetration through these holes, were clearly visible. Extensive tenting of the dura was seen in all subjects. It was impossible to force an 18-gauge epidural catheter through the dural hole after a single dural puncture made by a 25-gauge spinal needle. After multiple (five) dural punctures with the spinal needle, the epidural catheter penetrated the perforated dura in 1 of 20 cases. The epidural catheter penetrated the dural hole made by the Tuohy needle in 9 of 20 cases. The distribution of fat, rather than any dorso median connective tissue band, influences the course of epidural catheter in epidural space.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Spinal antinociception: clinical aspects.

Recent research has demonstrated the increasing importance of the spinal cord in processing and modulating nociceptive input. Different groups of drugs, each acting by a unique mechanism, have been shown to block nociceptive afferent transmission. None of the currently available spinally administered local anesthetics, opioids or non-opioids produce analgesia without side effects. Non-opioids such as alpha-2-adrenergic agonists may be more suited as adjuvants rather than sole analgesic agents and their main role lies in reducing the dose requirements of other analgesics. Spinal somatostatin and ketamine may have neurotoxic potential. The role of these drugs and of midazolam in pain management appears to be limited. Preliminary results suggest that the neuropeptide octreotide has potent analgesic effects. 'Balanced spinal analgesia' using a combination of low doses of drugs, with separate but synergistic mechanisms of analgesia, may produce the best results. The optimal drug combinations and dosages remain to be determined. It is essential that animal neurotoxicity studies followed by controlled clinical trials are performed before widespread spinal administration of new drugs.

Adrenergic alpha-Agonists↗
PubMed1995

Analgesia technique and post-operative morbidity.

Good analgesia does not normalize post-operative pulmonary function but is important in allowing measures such as post-operative physiotherapy to be applied following major abdominal or thoracic surgery. Clinical studies have generally failed to duplicate animal work on the effectiveness of pre-emptive analgesia possibly because the nociceptor stimuli persist as long as there is wound pain. Anaesthetic techniques which include sensory blockade are associated with a lower incidence of several post-operative complications and this improvement is more marked in high-risk patients. The contributions of spinal opioids to this is not known. Long-lasting analgesia can be provided via a catheter inserted in a relevant neurovascular compartment. There is no evidence that multimodal 'balanced' analgesia offers any advantages in terms of improved outcome or reduction in adverse events. Whilst sophisticated methods for providing post-operative pain relief, such as PCA and PCEA, are highly effective, they are appropriate for only a minority of surgical operations. An Acute Pain Service can delivery a traditional intermittent opioid regime effectively at relatively low cost.

Analgesia↗
PubMed1994

Purification and characterization of S-adenosylmethionine-protein-arginine N-methyltransferase from rat liver.

A protein methylase I (S-adenosylmethionine-protein-arginine N-methyltransferase; EC 2.1.1.23), with a high specificity for recombinant heterogeneous nuclear ribonucleoprotein particle (hnRNP) protein A1, was purified from rat liver. The purification method is simple and rapid; a single initial step of DEAE-cellulose DE-52 chromatography resulted in a 114-fold enrichment from the cytosol, and subsequent Sephadex G-200 chromatography and f.p.l.c. yielded a homogeneous preparation. Ouchterlony double-immunodiffusion analysis indicated that the rat liver enzyme is immunologically different from an analogous enzyme from the calf brain, nuclear protein/histone-specific protein methylase I [Ghosh, Paik and Kim (1988) J. Biol. Chem. 263, 19024-19033; Rajpurohit, Lee, Park, Paik and Kim (1994) J. Biol. Chem. 269, 1075-1082]. The purified enzyme has a molecular mass of 450 kDa on Superose chromatography and 110 kDa on SDS/PAGE, indicating that it is composed of four identical-size subunits. The Km values for protein A1 and S-adenosyl-L-methionine were 0.54 x 10(-6) and 6.3 x 10(-6) M respectively. S-Adenosyl-L-homocysteine and sinefungin were effective inhibitors of the enzyme with Ki values of 8.4 x 10(-6) M and 0.65 x 10(-6) M respectively. Bivalent metal ions such as Zn2+, Mn2+ and Ni2+ were particularly toxic to the enzyme; at 1 mM Zn2+, 99% of the activity was inhibited. In addition, 50% of the enzyme activity was lost by treatment with 0.12 mM p-chloromercuribenzoate, indicating a requirement for a thiol group for enzyme activity. Glycerol, a compound often used to prevent enzyme inactivation, inhibited over 80% of the activity when present in the reaction mixture at a concentration of 20%.

Animals↗
PubMed1994

Intrathecal and epidural somatostatin for patients with cancer. Analgesic effects and postmortem neuropathologic investigations of spinal cord and nerve roots.

BACKGROUND: The antinociceptive effects of somatostatin (SST) after intrathecal administration in rats and dogs and analgesic effects after intrathecal or epidural administration in humans were described previously. In this study, we seek to determine the efficacy of SST in cancer pain management and its potential neurotoxicity. METHODS: Eight patients with intractable cancer pain were studied. Pain intensity was assessed by patients on a four-grade scale (severe, moderate, mild, none). Additional analgesic drug requirements before and concomitant with SST treatment were used to evaluate the pain relief and assessed on a four-grade scale (poor, fair, good, or excellent). Spinal cords of five patients were autopsied. RESULTS: The mean duration of SST treatment was 11.3 days. The mean daily dose was 1,252 micrograms (range 250-3,000 micrograms). In six patients the pain relief was rated "excellent" or "good" and in two patients it was assessed "poor" or "fair". None of the patients demonstrated any evidence of neurologic deficit related to the SST treatment. At autopsy, two patients exhibited a moderate demyelination of some spinal dorsal roots and one patient also had a slight demyelination of the dorsal columns. CONCLUSIONS: SST administered intrathecally and epidurally was an effective analgesic in patients with terminal cancer. Because the described neuropathologic changes could also be cancer-related or result from chemotherapy or radiation therapy we suggest that further judicious use of SST is justified in this category of patients, if their pain remains unrelieved despite large doses of opioid analgesics.

Adult↗
PubMed1994

Combined spinal-epidural block in obstetrics.

Although epidural and spinal blocks are well-accepted regional techniques in obstetrics, they have several disadvantages. Combined spinal-epidural (CSE) technique reduces or eliminates the risks of these disadvantages. The sequential CSE technique can reduce the incidence and severity of maternal hypotension. CSE block combines the rapidity, density and reliability of spinal block with the flexibility of continuous epidural to extend the duration of analgesia. It has been used in thousands of patients without any reports of major problems. Catheter penetration through the dural hole though unlikely is not impossible. Before any injection in the epidural catheter, its position should always be confirmed by aspiration test. The technique should be used only by those who are experienced in spinal and epidural blocks. CSE is an important addition to the armamentarium of the obstetric anaesthesiologist.

Analgesia, Epidural↗
PubMed1994

Postoperative pain and its management.

In recent years tremendous progress has been made in our understanding of peripheral, spinal cord and brain mechanisms involved in acute pain and in the neurophysiologic description of nociceptive pathways, receptors and mediators. Great strides have been made in our knowledge of pharmacokinetics and pharmacodynamics of drugs used to treat pain. However, in spite of unprecedented interest in pain and its management, most patients undergoing surgery still receive treatments that have changed little in the past decades. Untreated severe postoperative pain has many deleterious effects on respiration, circulation, autonomic activity, renal function and gastrointestinal activity. The technique of pain control does have a significant influence on postoperative complications particularly in high risk patients undergoing major surgery. Today we have a variety of effective modalities to control postoperative pain. These include different opioid administration techniques such as spinal opioids (epidural, intrathecal), patient controlled analgesia (i.v., subcutaneous, epidural), i.v. infusions, sublingual, oral transmucosal ("lollipop"), rectal, nasal, intra articular. Non-opioid analgesics such as non-steroidal anti-inflammatory drugs and alpha-adrenergic agents (systemic, epidural, intrathecal) are available. Various combinations of the above are also possible. However, it is increasingly recognised that the solution to the problem of inadequate pain relief on surgical wards lies not so much in the development of new drugs and new techniques but in the development of a formal organisation for better use of existing drugs and techniques. A simple, low-cost organisation model for acute pain services (APS) is described.

Adult↗
PubMed1994

Sequential combined spinal epidural block versus spinal block for cesarean section: effects on maternal hypotension and neurobehavioral function of the newborn.

Sequential combined spinal-epidural (CSE) block was compared with spinal block for elective cesarean section. The quality of surgical analgesia and the effect on maternal blood pressure and neonatal neurobehavioral function were evaluated. Forty-two healthy parturients were randomly divided into a spinal (n = 21) and a sequential CSE (n = 21) group. A T4 sensory block was targeted. In the spinal group, 0.5% hyperbaric bupivacaine, 2.5 mL, was injected into the subarachnoid space through a 26-gauge Quincke needle. In the sequential CSE group, 1.5 mL of 0.5% hyperbaric bupivacaine was injected into the subarachnoid space through a long 26-gauge Quincke needle, which was introduced through an 18-gauge Tuohy needle. An epidural catheter was then inserted. If the block in the sequential CSE group did not reach the T4 level in 15 min, it was extended by fractionated doses of 0.5% bupivacaine administered through the epidural catheter. Ephedrine, 10 mg intravenously (i.v.), was given to treat hypotension (20% decrease from baseline value and/or systolic blood pressure below 100 mmHg). The time intervals from induction of block to start of surgery and to delivery were shorter in the spinal group (P < 0.01). Cephalad spread of block (pinprick) 15 min after induction was T4 [T2-T7] (median [range]) in the spinal group and T7 [T2-L1] in the sequential CSE group (P < 0.05). All patients in the sequential CSE group needed epidural bupivacaine, 53.8 +/- 6.5 mg (mean +/- SEM). The surgical analgesia was good or excellent in both groups before delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Combined spinal epidural block versus spinal and epidural block for orthopaedic surgery.

In a controlled study a single segment combined spinal epidural (CSE) block was compared with spinal or epidural block for major orthopaedic surgery. Seventy-five patients, age 52-86 yr, were randomly assigned to receive one of the three blocks. Bupivacaine 0.5% was used for surgical analgesia. The postoperative pain relief after 4.0 mg epidural morphine was compared with the analgesic effect of 0.2 or 0.4 mg morphine administered intrathecally. With the spinal technique good or excellent surgical analgesia and muscle relaxation were achieved rapidly (11.8 +/- 1.1 min). The time taken to provide an equally effective and reliable block with the CSE technique was no longer (14.9 +/- 2.2 min). For epidural block with the catheter technique more time was required (35.9 +/- 3.9 min) to provide acceptable surgical conditions (P < 0.05). Perioperative sedatives and concomitant analgesics were required more frequently and in larger doses by the patients undergoing surgery with epidural block (P < 0.05) than with CSE or spinal block. Our study demonstrated that the analgesia after surgery provided by 0.2 and 0.4 mg morphine administered intrathecally was comparable to that provided by 4.0 mg of epidural morphine. It is concluded that the analgesia and surgical conditions provided by the spinal and CSE blocks were similar and were superior to those provided by an epidural block.

Aged↗
PubMed1993

Improvement in i.v. regional anaesthesia by re-exsanguination before surgery.

A modification of an i.v. regional anaesthesia (IVRA) technique is described in which the arm is re-exsanguinated before surgery (re-IVRA). IVRA and re-IVRA were compared for quality of operative field, sensory and motor block, quality of analgesia and blood concentrations of prilocaine, lignocaine and mepivacaine in a double-blind study in 120 patients undergoing hand surgery. Re-IVRA provided a significantly better surgical field without affecting sensory or motor block. Re-exsanguination improved tolerance of the tourniquet. Plasma concentrations in the re-IVRA group showed some increases, but these were not in the toxic range.

Adolescent↗
PubMed1993

A clinical and laboratory study to compare the addition of 0.2 mg of morphine, 0.2 mg of epinephrine, or their combination to hyperbaric bupivacaine for spinal anesthesia in cesarean section.

The aim of this prospective, randomized, double-blind study was to compare the effects of adding either preservative-free morphine, 0.2 mg (n = 20), epinephrine, 0.2 mg (n = 21), or a combination of both (n = 29) to hyperbaric bupivacaine in parturients having elective cesarean sections during spinal anesthesia. Ten additional patients receiving spinal bupivacaine alone were studied as the Control Group. High-pressure liquid chromatography with a sensitivity of 20 micrograms/mL was used to measure serum bupivacaine in all subjects. The results showed that the spread and regression of the sensory and motor blocks were similar among the study groups. However, the intraoperative analgesia was superior in patients receiving bupivacaine combined with morphine and epinephrine, whereas there was no difference between those given an addition of either morphine or epinephrine. Postoperative analgesia was the shortest and opioid requirement in the first 24 h the most with epinephrine alone. No respiratory depression occurred. The neonatal condition was excellent in all groups. Serum concentrations of bupivacaine at 10 min, at delivery (25 +/- 1.4 min), and at 60 min after the intrathecal injection were similar among the groups including the Control Group. The concentrations of bupivacaine in umbilical arterial and venous sera were less than the sensitivity level of the analytical method. We conclude that the addition of 0.2 mg of morphine plus 0.2 mg of epinephrine to hyperbaric bupivacaine improves the intra- and postoperative analgesia without an added risk. This improvement is not due to vasoconstriction and a reduction in the absorption of bupivacaine from the subarachnoid space.

Adult↗
PubMed1992

Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain.

The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN'G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found in MBP; however, their relative concentrations varied significantly with the age of the animal. The amounts of MeArg and Me2(sym)Arg in MBP increased as a function of the age of the brain, whereas that of Me2(asym)Arg decreased. MBP from early-myelinating mouse brain was shown to contain a high proportion of Me2(asym)Arg, which was hardly detectable in older brain MBP. This derivative, Me2(asym)Arg, was also absent from MBP embedded in the most compact multilamellar myelin, but was present in MBP in the least compact myelin (P3B). Comparing the extent of total methylation in vivo (sum of all three arginine derivatives), MBP extracted from less-compact myelin (P3A and P3B) showed a level approx. 40% higher than that from compact myelin. MBPs isolated from dysmyelinating mutant mouse brains, such as jimpy (jp/y) and quaking (qk/qk), contained a much higher level of Me2(asym)Arg relative to the other two methyl derivatives and also in comparison with those levels in the mother brain MBP. SDS/PAGE analysis of MBPs extracted from the mutant (both jp/y and qk/qk) as well as young normal (6-13 days old) mouse brains indicated the presence of a high-molecular-mass isoform of MBP (about 32 kDa), but this isoform was not found in adult brains. These results therefore indicate that structural integrity of myelin membrane in which MBP is embedded appears to play a pivotal role in determining the extent and the kind of Me2Arg formation in MBP at the post-translational level.

Animals↗
PubMed1991

Enzymic methylation of myelin basic protein in myelin.

Myelin fractions with different degrees of compaction were isolated from bovine brain, and post-translational methylation of membrane-associated proteins was studied. When the purified myelin-basic-protein-specific protein methylase I and S-adenosyl-L-[methyl-14C]methionine were added exogenously, the most compact myelin fraction exhibited higher methyl-accepting activity than the less compact dense fractions. The methylated protein was identified as myelin basic protein (18.4 kDa) exclusively among the several myelin proteins from all membrane fractions, by SDS/PAGE/radioautography of methyl-14C-labelled membrane proteins. The methyl-14C-labelled amino acid residue in the basic protein was identified by h.p.l.c. as NG-methylarginine, indicating the high degree of specificity for the arginine residue as well as the myelin basic protein in the intact myelin membranes. The possibility of a charge alteration of myelin basic protein resulting from its arginine methylation was investigated by using the purified component 1 of myelin basic protein. The methylated component was shown to be less cationic than the unmethylated component by Bio-Rex 70 cation-exchange chromatography, since the former preceded the latter. However, in the presence of the denaturant (guanidinium chloride), the two species were co-eluted, indicating that the charge difference between methylated and unmethylated myelin basic protein can only be shown under the renatured condition.

Amino Acids↗
PubMed1991

An enzyme-linked immunosorbent assay for myelin basic protein-specific protein methylase I.

A sandwich enzyme-linked immunosorbent assay (ELISA) has been developed to determine myelin basic protein (MBP)-specific protein methylase I. Rabbit immunoglobulin anti-bovine MBP-specific protein methylase I, purified by Sepharose-A affinity chromatography, was utilized as the primary antibodies, while the same antibodies which had been conjugated to peroxidase were employed as the indicator antibodies. This assay method was about 280 times more sensitive than the conventional trichloracetic acid (TCA) precipitation method. Employing the ELISA, the level of MBP-specific protein methylase I during mouse brain development was examined; the peak level of the methylase was shown to be at 16th postnatal day, indicating temporal correlation with myelination. Among several species of brains examined, human showed the highest and carp the least amount of MBP-specific protein methylase I; 6.33 micrograms and 0.33 micrograms per mg of brain cytosol protein, respectively. Dysmyelinating jimpy hemizygous mouse brain showed the immunoreactive MBP-specific protein methylase only 60% that of the control at 20 days of age. The high sensitivity of the method together with the fact that MBP-specific protein methylase is present in human cerebrospinal fluid suggests a possible clinical application of this method for evaluating demyelinating disorders.

Animals↗
PubMed1991

Intrathecal morphine 0.2 mg versus epidural bupivacaine 0.125% or their combination: effects on parturients.

To compare the efficacy and side effects of 0.2 mg intrathecal (IT) morphine with 0.125% epidural bupivacaine, 62 women in labor were studied. They were randomly divided into three groups: group 1 (n = 20) received IT morphine; group 2 (n = 22) received epidural bupivacaine; and group 3 (n = 20) received a combination of both using a combined spinal-epidural (CSE) technique. According to a visual analogue scale for assessing analgesia, neither IT 0.2 mg morphine nor 10 ml 0.125% epidural bupivacaine was effective in producing adequate pain relief in labor, whereas the combination produced excellent analgesia. The use of IT morphine significantly reduced the dosage requirement of epidural bupivacaine. The incidence of nausea, vomiting, and pruritus was significantly higher when IT morphine had been administered, whereas that of urinary retention did not differ. No serious respiratory depression occurred in any of the patients. When the course of labor was studied, the prior use of IT morphine significantly prolonged the duration of the first stage of labor and the total duration of labor. We conclude that the administration of 0.2 mg IT morphine in combination with epidural administration of 0.125% bupivacaine provides better analgesia than the administration of either drug alone.

Adult↗