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Biomedical subjects

P P Raj

Publications and source records attributed to P P Raj.

At least 19 recordsLinked to original sources

Visceral pain.

Visceral pain, which originates from organ tissues of the thorax, abdomen or pelvis, is generally perceived as a deep, dull and vague sensation; in most cases it cannot even be clearly described, being a sense of discomfort, malaise or oppression rather than real pain. Crushing, cutting and burning generally have no algogenic effect in the viscera whereas mechanical stimulation, ischemia and chemical stimulation, separately or in combinations, may cause pain. With these characteristics, visceral pain differs from somatic pain. The characteristics of visceral pain, perception and transmission of painful visceral stimuli are explained, some common visceral pain syndromes are presented and sympathetic neurodestructive approaches as a treatment option are described in this review.

Abdominal Pain↗

Spinal cord stimulation: a comparison of efficacy versus other novel treatments for refractory angina pectoris.

Recently much attention has been directed toward novel treatment alternatives for refractory angina pectoris. Refractory angina is persistent stable class III or IV angina despite maximally tolerated medical treatment in patients with end-stage coronary artery disease. Transmyocardial laser revascularization (TMLR), gene therapy, intermittent urokinase therapy, enhanced external balloon counterpulsation, and spinal cord stimulation have all been employed to treat refractory angina pectoris. TMLR and gene therapy are invasive open-chest procedures that have yielded controversial results. Intermittent urokinase and enhanced external balloon counterpulsation studies have limited follow-up times and require multiple clinic visits for treatment. Spinal cord stimulation has a proven short- and long-term efficacy and cost-effectiveness in the treatment of refractory angina. When compared to coronary artery bypass grafting (CABG), it has been shown to decrease the frequency of anginal attacks and consumption of short-acting nitrates to the same extent in refractory angina. Spinal cord stimulation's safety profile has also been well established and it can be used concurrently with cardiac pacemakers or MRI systems, provided the proper precautions are taken. Since spinal cord stimulation is a minimally invasive procedure with a favorable efficacy and safety profile, it should be considered as a valid treatment alternative after medical management has failed in refractory angina prior to implementing invasive modalities such as TMLR or gene therapy.

Journal Article↗

Painless electrodiagnostic current perception threshold and pain tolerance threshold values in CRPS subjects and healthy controls: a multicenter study.

The purpose of this study is to evaluate both painless and painful sensory transmission in patients with Complex Regional Pain Syndrome (CRPS) using the automated electrodiagnostic sensory Nerve Conduction Threshold (sNCT) test. This test generates reliable, painless Current Perception Threshold (CPT) and atraumatic Pain Tolerance Threshold (PTT) measures. Standardized CPT and PTT measures using constant alternating current sinusoid waveform stimulus at 3 different frequencies 5 Hz, 250 Hz, and 2 kHz (Neurometer CPT/C Neurotron, Inc. Baltimore, MD) were obtained from CRPS subjects at a distal phalange of the affected extremity and at an ipsilateral asymptomatic control site. Matched sites were tested on healthy subjects. Detection sensitivities for an abnormal PTT and CPT test were calculated based on specificity of 90% as determined from data obtained from healthy controls. A Spearman rank correlation was used to test for a significant association between presence of allodynia and an abnormal PTT or CPT at any frequency tested. Thirty-six CRPS subjects and 57 healthy controls were tested. The highest detection sensitivity of the PTT test from symptomatic test sites was 63% for the finger and 71% for the toe. PTT abnormalities were also detected, to a lesser degree, at the asymptomatic control site (41% finger control site, 16% toe control site). The highest CPT detection sensitivity at the symptomatic site was 37% for the finger site and 53% for the toe site. CPT abnormalities were also detected at the asymptomatic control site (29% finger control site, 37% toe control site). Eighty-six percent of the CRPS subjects had either a PTT or CPT abnormality at any frequency at the symptomatic site. There was a significant correlation between presence of allodynia and presence of an abnormal CPT and PTT, respectively (P < .01). The correlation coefficient was lower for CPT than for PTT, ie, 0.34 versus 0.6 for the finger and 0.48 versus 0.67 for the toe, respectively. In studied CRPS patients an abnormal PTT was detected with higher sensitivity than an abnormal CPT. Assessing PTT may become a useful electrodiagnostic quantitative sensory test for diagnosing and following the course of neuropathic pain conditions.

Journal Article↗

Behavioral and histopathologic effects following intrathecal administration of butorphanol, sufentanil, and nalbuphine in sheep.

A large number of opioids and nonopioids have been administered epidurally and intrathecally in the hope of providing segmental analgesia without serious adverse effects. However, neurotoxicity data are generally unavailable for many of these drugs. The present study evaluated the behavioral, motor, electroencephalographic, and histopathologic changes following intrathecal injection of large and small doses of butorphanol, sufentanil, and nalbuphine in sheep. Thirty-two sheep (20-32 kg) were anesthetized and catheters placed intrathecally after hemilaminectomy. The large doses of butorphanol, sufentanil and nalbuphine were 0.375 mg/kg (4.4-5.2 ml), 7.5 micrograms/kg (3.6-4.8 ml) and 0.75 mg/kg (1.5-2.4 ml), and the small doses were 0.075 mg/kg (0.9-1.1 ml), 1.5 micrograms/kg (0.7-0.9 ml) and 0.15 mg/kg (0.38-0.5 ml), respectively. The opioids were administered intrathecally every 6 h for 3 days and the above-mentioned parameters studied. Five sheep received intrathecal saline (1.1 or 5.2 ml) and served as controls. Histopathologic changes were evaluated by a neuropathologist blinded to the study protocol. Irrespective of dose, intrathecal injection of butorphanol was associated with severe behavioral responses such as agitation, rigidity, vocalization, and restlessness, as well as prolonged or irreversible hindlimb paralysis. Electroencephalography showed increased cortical activity or seizure activity. One sheep died because of severe respiratory depression that did not respond to naloxone. Spinal cord histologic changes consisted of suppurative meningitis and myelitis as well as neuronal changes such as spongiosis and chromatolysis. Large doses of intrathecal sufentanil were associated with similar though somewhat less severe responses. The behavioral and motor changes following the small dose of intrathecal sufentanil were of mild to moderate nature. Following intrathecal nalbuphine, the above-mentioned changes were similar to those seen in control animals. We conclude that butorphanol in doses of 0.075 and 0.375 mg/kg intrathecally and sufentanil 7.5 micrograms/kg intrathecally are neurotoxic in sheep.

Animals↗

Pharmacokinetics of continuous intravenous infusion of methadone in the early post-burn period.

The pharmacokinetics of methadone were studied in 14 patients with acute, severe burns and receiving an intravenous infusion of methadone to control their pain. Serum methadone concentrations were measured by gas chromatography on 5 mL arterial blood samples obtained at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0 and 24 hours after the start of infusion. Albumin and Alpha-1-Acid glycoprotein (AAG) were measured by radial immunodiffusion. Serum methadone concentration-time data were fit with the appropriate sum of exponentials equation using iterative nonlinear regression analysis. All serum methadone concentration-time data were best described by a monoexponential equation. Estimates of Vd (180 +/- 62 L) were not significantly different from those predicted for Vc from body weight using literature values (156 +/- 41). Estimates of Vd were, however, significantly lower than those predicted for Vz using literature values (282 +/- 74) (P less than 0.001). In addition, CL values (53.0 +/- 19.3 L/h) were significantly higher than those predicted from body weight using literature values (9.2 +/- 2.3 L/h) (P less than 0.001). These changes resulted in estimates of the elimination half-life for methadone of 2.6 +/- 1.1 h. Methadone protein binding was independent of both albumin and AAG concentration. Multiple regression demonstrated that the significant predictors of CL in the early post burn injury period were serum albumin, days post injury and age. The coefficient of determination (r2) for this model was 0.8190. In summary, methadone CL is markedly elevated while the Vc is essentially unchanged during the early post burn injury period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

SRK II formula in the calculation of intraocular lens power.

We studied 400 eyes which underwent cataract extraction with posterior chamber intraocular lens (IOL) implantation to compare the predictive accuracy of various IOL power calculation formulae. The new Sanders-Retzlaff-Kraff (SRK) II formula was more accurate than the original SRK and Binkhorst II formulae. Modification of the A constants used in the SRK II formula to make it 'surgeon specific' improved its performance further; 80% of the eyes had less than 1 dioptre error and only one eye (0.3%) had an error of more than 3 dioptres.

Humans↗

Influence of acetylator phenotype of the leprosy patient on the emergence of dapsone resistant leprosy.

The half time of disappearance of dapsone and monoacetyl dapsone and the acetylator phenotype of the leprosy patients who harboured dapsone sensitive and dapsone resistant M. leprae was assessed in 27 subjects. Sixteen patients were rapid acetylators, five were slow and six were intermediate acetylators. The mean T 1 1/2 lives of dapsone (30.26 +/- 11.0) and monoacetyl dapsone (31.11 +/- 12.0) were also studied in the above patients. The percentage of different acetylators in both resistant and sensitive groups were similar showing no correlation between the emergence of drug resistance and the phenotype of the patient. The mean time of disappearance of DDS and MAD in the different acetylators did not show significant difference. The ratios of MAD/DDS in an individual at 3, 6 or 24 hours after the dose were similar. The mean T 1 1/2 lives of DDS and MAD in resistant and sensitive patients also showed no difference. Neither T 1 1/2 lives of DDS or MAD nor the acetylator phenotype seem to influence the emergence of dapsone resistance.

Acetylation↗

Secondary and primary dapsone resistant leprosy: an analysis of 199 patients from St. Thomas Hospital and leprosy project, Chettupattu, South India.

The occurrence of secondary and primary dapsone resistance in 199 patients in our control area and the influence of certain variables such as age, initial bacteriological and morphological indices, duration of regular dapsone monotherapy, on the emergence of dapsone resistance was investigated. Ninety one of 122 patients and 29 out of 77 showed secondary (SDR) and primary (PDR) resistance to dapsone respectively. Very low BI (BI:2.5) group also showed both SDR (60%) and PDR (40%). Low or high MI group exhibited the same degree of resistance. Multiplication of M. leprae was obtained even when the MI of the inocula was zero. Even in the group who had 1 to 5 years duration of regular dapsone treatment, 85% patients showed SDR. Significance of such results are discussed in relation to chemotherapy. The overall minimum prevalence of SDR was found to be 5.6% and 21% in the case of PDR in our control area.

Age Factors↗

Certain aspects of dapsone metabolism in leprosy patients as studied by high performance liquid chromatography (HPLC) and qualitative screening tests.

Dapsone (DDS) in urine of 250 leprosy patients collected on surprise visits were screened by simple paper spot, tile tests and sensitive Enzyme linked immunosorbent assay (ELISA) and Haemagglutination inhibition (HI) tests. The urinary DDS concentration as well as DDS/C ratios were also studied. Simultaneously, 50 microliter of blood was collected from each of these patients and its dapsone content was estimated by HPLC. Urine samples with means of 25 to 30 micrograms/ml DDS and 55-64 micrograms/mg DDS/C ratios were found to give positive tests by any of the above screening procedures, while their mean blood DDS concentration was found to be 0.91 microgram/ml. The corresponding values for those specimens giving negative tests were 3.8 to 5.7 micrograms DDS per ml and 9 to 13 micrograms/mg DDS/C ratio. The blood DDS concentration in this group was ranging from 0.16 to 0.18 micrograms/ml. The findings are discussed in relation to their metabolic significance and their application in a leprosy control programme.

Chromatography, High Pressure Liquid↗

Comparison of continuous epidural infusion of a local anesthetic and administration of systemic narcotics in the management of pain after total knee replacement surgery.

Continuous bupivacaine epidural analgesia was compared with conventional methods of systemic analgesic administration in the management of postoperative pain in 30 patients for 3 days following total knee replacement surgery. Patients given continuous epidural analgesia had significantly better pain relief (visual analogue scale, global evaluation), needed significantly fewer supplementary analgesics, and had significantly fewer side effects. In the epidural group, sensory block averaged six dermatomes on day 1 and four dermatomes on day 3. The number of patients with complete (or almost complete) motor block of the lower limbs decreased from eight on day 1 to five on day 3. The mean dosage of bupivacaine decreased from 21.0 +/- 5.7 (SD) mg/hr on day 1 to 15.1 +/- 8.5 mg/hr on day 3. No signs of accumulation of or toxic reactions to bupivacaine were seen.

Adolescent↗

Transcutaneous electrical nerve stimulation and myoneural injection therapy for management of chronic myofascial pain.

The purpose of this article has been to discuss in detail both the rationale and techniques for TENS and myoneural injection therapy as modalities for the management of chronic myofascial pain. In a more subtle sense, we have also interjected some of our philosophy regarding the treatment of chronic myofascial pain. As was discussed earlier in the text of this article, very seldom, if ever, will any single technique stand alone as a "cure" for the patient with chronic pain, but, instead, each modality must be considered as an adjunctive form of multidisciplinary care. The multidisciplinary approach to pain management includes, as a minimum, pharmacotherapy, physical therapy, and behavioral medicine therapy. The concept of the team approach and goals of management, rather than cure, for chronic myofascial pain, cannot be overstated and is often as difficult to impart to the clinician as it is to the patient. To employ any individual form of therapy, the clinician must understand the indications and limitations of each modality in a total treatment program. Over the last several years TENS therapy has become extremely popular to a large extent because it is a noninvasive technique that most patients can be taught to use safely and effectively. An additional advantage to TENS therapy is that it provides many patients with some means of control over their pain, independent of medications and hands-on therapy by health care providers. Myoneural block therapy is often utilized to add a measure of control over the severe pain and dysfunction that may be present during the early phases of active treatment of chronic myofascial pain. It is used to enhance the effects of a conservative multidisciplinary pain management program when utilized on a short-term basis. Myoneural block therapy is often a useful adjunct to physical therapy to improve the patient's overall range of motion and facilitate either treatment by the physical therapist or a home exercise program. The clinician is reminded that myoneural injection therapy can be overutilized. It should be limited as to the number of injections per visit. Also, the total number of visits the patient receives injections should be kept low. After the initial myoneural injection treatment series of three to five sessions, it should be utilized only for severe pain exacerbation that has been unresponsive to conservative, noninvasive management.

Anesthetics, Local↗

Pain clinic #8. Patient-controlled analgesia for postoperative pain in orthopaedic patients.

Patient-controlled analgesia for pain management following orthopaedic surgery was evaluated subjectively by 22 patients and 11 nurses. Half of the patients received morphine and half received meperidine. No difference was found in the amount of drug used between groups. Although pain was never completely relieved, 91% of patients experienced only mild pain or were mildly comfortable with the technique. All patients reported a high satisfaction with patient-controlled analgesia and all nurses ranked the technique as good to excellent. Eight-six percent of patients who had previously used another type of pain management ranked patient-controlled analgesia superior.

Adolescent↗

Peripheral neurotoxicity of 2-chloroprocaine and bisulfite in the cat.

The responses of peripheral nerves less than 6 hr after and 2 weeks after exposure to 2-chloroprocaine (2-CP) and bisulfite (BS) were studied in cats using electrophysiologic techniques and by light and electron microscopy. Three percent 2-CP with 0.07% or 0.2% BS was not toxic to peripheral nerves. Three percent 2-CP with 1.2% BS and 1.2% BS (pH 2.8) alone had an acute effect on the peripheral nerves but no chronic effect. Ten percent BS (pH 2.8) caused Wallerian degeneration. However, at pH 4.8, no chronic toxicity was observed. Using conductivity measurements, it was shown that 2-CP and BS, when mixed, form an ion pair in solution that lowers the effective concentration of BS.

Action Potentials↗

Influence of bupivacaine on mepivacaine protein binding.

To elucidate the mechanism of any drug displacement interaction, we examined the protein binding of mixtures of mepivacaine and bupivacaine in serum and solutions of albumin or alpha 1-acid glycoprotein. Protein binding data with mepivacaine alone were best described by a model with one class of binding site and a partitioning constant in serum and by a model with one class of binding site in both isolated protein solutions. Binding affinity of mepivacaine in serum was reduced in the presence of bupivacaine. Displacement of mepivacaine by bupivacaine was observed when an alpha 1-acid glycoprotein solution was studied. Classic competitive inhibition was demonstrated. Bupivacaine reduced mepivacaine binding to albumin, but the degree of displacement was not significant. When administered simultaneously, these two amino-amide local anesthetics interact synergistically to produce a higher than expected free concentration of mepivacaine. This interaction increases the risk of toxicity.

Binding, Competitive↗