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Biomedical subjects

T Khan

Publications and source records attributed to T Khan.

At least 55 records · Page 3Linked to original sources

Do direct current electric fields enhance micturition in the spinal cat?

Changes in micturition behavior and motoneuron ultrastructure were studied in spinal cats to determine the effects of direct current (DC) electric field treatment. Adult cats received a complete injury at T8. A treatment group with an implanted 15 microA DC source and electrodes positioned near the lesion site was compared with non-treatment groups that were either operated or unoperated. Both bladder emptying with Crede and the withdrawal reflex were improved in the treatment group compared with the non-treatment group. Urodynamic procedures showed that high urethral resistance and pelvic floor activity following spinal injury was partially reduced in the stimulated cat, indicating inhibition of the urethral sphincter. The ultrastructural analysis of Onuf's nucleus suggested a similar synaptic input in all three groups. In conclusion, possible activation of inhibitory processes and/or neural plasticity best explain the early improvement of bladder function seen following electrical stimulation.

Animals↗

Electrophysiological improvement after co-implantation of carbon filaments and fetal tissue in the contused rat spinal cord.

The electrophysiological integrity of the adult rat spinal cord was assessed at the lumbar, lower cervical and cortical levels after the animals sustained a severe contusion injury at the mid-thoracic level (T8) and received either carbon filament cultured with fetal spinal cord tissue implants, fetal tissue implants, or carbon filament implants alone. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were recorded from all animal groups at the end of the 8-week survival period. The results of this study demonstrate that the spinal cord injured animals that received carbon filament cultured with fetal spinal cord tissue implants had the highest degree of electrophysiological recovery, indicating that this combination plays an important role in promoting recovery after injury.

Animals↗

Effectiveness of the lactational amenorrhea method in Pakistan.

OBJECTIVE: To determine the efficacy of the lactational amenorrhea method of family planning (amenorrhea during full or nearly full breastfeeding for 6 months postpartum). DESIGN: Prospective noncomparative study. SETTING: Normal breastfeeding women in Karachi and Multan, Pakistan, most delivered at home by a midwife. PATIENTS: Three hundred ninety-nine newly delivered mothers who successfully had breastfed a previous child and chose the lactational amenorrhea method to prevent a subsequent pregnancy, 391 of whom were followed for a full year. INTERVENTIONS: Mothers were taught, before or shortly after delivery, to use the method and were interviewed in their homes each month by a Lady Health Visitor. MAIN OUTCOME MEASURE: Life-table pregnancy rates. Periods of postpartum or lactational abstinence were excluded in the calculation of the pregnancy rates. RESULTS: During full or nearly full breastfeeding, while the women were amenorrheic and not otherwise contracepting, the rate of pregnancy was 0.6%. The pregnancy rate during lactational amenorrhea alone was 1.1% at 1 year postpartum. CONCLUSION: The lactational amenorrhea method was found to be highly effective for 6 months. A high degree of contraceptive protection endures for a full year during lactational amenorrhea, but not after the return of menses during breastfeeding.

Adolescent↗

Evaluation of a thin-film peripheral nerve cuff electrode.

This is a study of the reaction of large nerves to implantation using a flexible, thin-film cuff electrode. Cuff electrodes were implanted on the sciatic nerve of three cats. An implantation period of six weeks allowed sufficient time for any injury responses in the nerve and connective tissue sheath around the cuff to develop. The electrode came off the nerve in one of the cats. In the remaining two cats, gross observation following explantation of the electrodes revealed encapsulation of the cuffs without swelling of nerve tissue. Histological evaluation did not demonstrate nerve injury. The nerve cuff electrodes, which are comprised of titanium and iridium coatings on a fluorocarbon polymer substrate, appeared unaffected by the implantation, and connective tissue encapsulation did not adhere to either the polymer substrate or metallization. Evaluation of the electrodes using activated iridium oxide charge injection sites in more extended studies is now being undertaken.

Animals↗

DNA synthesis precedes gliotoxin-induced apoptosis.

The toxin gliotoxin induces apoptosis or programmed cell death in a variety of immune cells including thymocytes. Apoptosis induced by gliotoxin in thymocytes is unaffected by protein synthesis inhibitors nor is it associated with early changes in intracellular calcium levels (Beaver and Waring, 1994). This work shows that the cell lines P815 and WEHI7 and murine thymocytes when treated with gliotoxin show an early incorporation of tritiated thymidine over the concentration range which causes apoptosis. Proliferating cell nuclear antigen (PCNA), a marker for S phase, is elevated in cells following gliotoxin treatment and S phase DNA content is increased. Thymidine incorporation is inhibited by hydroxyurea, an inhibitor of replicative DNA synthesis not repair. Free radical scavangers have no effect on apoptosis induced by gliotoxin in thymocytes. Hydrogen peroxide-treated cells showed no enhanced thymidine incorporation and no apoptosis. Thus oxidative stress does not appear to be a factor in gliotoxin-induced apoptosis. Thymocytes treated with gliotoxin show increased phosphorylation of a 16.3 kDa protein, and apoptosis is inhibited by the tyrosine kinase inhibitor genistein, which also inhibited the increased thymidine incorporation in P815 cells. We conclude that one mechanism by which gliotoxin can cause apoptosis may be the induction of inappropriate entry of cells into the cell cycle followed by death.

Journal Article↗

Distribution of alpha 1 subunit isoform of (Na,K)-ATPase in the rat spinal cord.

Three isoforms of the alpha subunit of (Na,K)-ATPase have been identified in the rat central nervous system. Using a probe specific for the alpha 1 isoform, mRNA levels were measured from five sections of the rat spinal cord using slot blot techniques. Assigning a value of 1 to the slope obtained from the cervical section, the upper thoracic section was 2.6 times higher; the midthoracic section was 4.5 times higher; the lower thoracic section was 2.6 times higher; and the lumbar section was 1.7 times higher. The results suggest that alpha 1 isoform mRNA levels are not uniform throughout the spinal cord. In situ hybridization techniques showed that alpha 1 isoform mRNA was diffusely abundant in glial and central canal ependymal cells, while labeled neurons were localized exclusively in laterally located anterior horn neurons in cervical, thoracic, and lumbar segments and in ventromedial neurons in mid-thoracic spinal cord. Also, dorsal root ganglia neurons were extensively labeled at all segments.

Animals↗

Electric field distribution within normal cat spinal cord.

Electric currents of small magnitude have been used successfully to induce regrowth of injured spinal cord fibers. The purpose of this study was to determine the potentials and current density distributions on the surface, as well as within the spinal cord, after the application of exogenous electric fields. A 10 microA DC current was applied epidurally to the spinal cord using two different electrode configurations. The two electrode configurations studied were: anode and cathode dorsal (D-D) and anode ventral and cathode dorsal (V-D). Two types of recording electrodes were used to map the potentials on the surface and within the spinal cord. The recording system consisted of glass microelectrodes connected to differential amplifiers. The output was recorded on a polygraph. The current density was more localized on the dorsal surface of the spinal cord for the D-D configuration. In contrast, in the V-D configuration, the current density was greater near the anode on the ventral surface and near the cathode on the dorsal surface of the spinal cord. As a result of the anode being located ventrally, there was a more uniform current density distribution within the spinal cord.

Animals↗

Electrical field distribution within the injured cat spinal cord: injury potentials and field distribution.

This study investigated the spontaneous injury potentials measured after contusion or transection injury to the cat spinal cord. In addition, the distribution of electrical field potentials on the surface and within the spinal cord were measured following applied electrical fields after transection and contusion injuries. After transection of the spinal cord, the injury potentials were -19.8 +/- 2.6 mV; after contusion of the spinal cord, the injury potentials were -9.5 +/- 2.2 mV. These potentials returned to control values within 2.5-4h after injury. The electrical field distribution measured on the dorsal surface, as well as within the spinal cord, after the application of a 10 microA current, showed little difference between contusion and transection injuries. Scalar potential fields were measured using two configurations of stimulating electrodes: dorsal to dorsal (D-D), in which both electrodes were placed epidurally on the dorsal surface of the spinal cord, and ventral to dorsal (V-D), in which one electrode was placed dorsally and one ventrally. As reported in normal uninjured cats, the total current in the midsagittal plane for the D-D configuration was largely confined to the dorsal portion of the spinal cord; with the V-D configuration, the current distribution was uniform throughout the spinal cord. In the injured spinal cord, the equipotential lines midway between the stimulating electrodes have a wider separation than in the uninjured spinal cord. Because the magnitude of the electrical field E is equal to the current density J multiplied by the resistivity r, this suggests that either the current density is reduced or that the resistivity is reduced.

Animals↗

Macrophage adherence prevents apoptosis induced by ricin.

Ricin, a lectin with potent protein synthesis inhibitory properties, has been known to cause morphological changes in epithelial cells typical of apoptosis (P. Waring et al., Med. Res. Rev. 11, 1-17 (1991)). In earlier preliminary experiments from this laboratory with murine macrophages and T-blasts (P. Waring, J. Biol. Chem. 265, 14,476-14,480 (1990)), it was shown that ricin induces regular DNA fragmentation, a biochemical event also associated with apoptosis. Here we confirm morphologically and by examination of DNA fragmentation that macrophages undergo apoptosis when treated with ricin in a dose-dependent manner. Ricin also inhibits adherence of macrophages to plastic surfaces but does not affect adherence of preadhered macrophages after 7 h of treatment. We also report that adherence significantly diminishes DNA fragmentation induced in macrophages by ricin but has no effect on ricin-induced inhibition of protein synthesis. From these results we may conclude that the property of ricin to induce apoptosis may not be related to its ability to inhibit protein synthesis in macrophages. Moreover, the anti-phagocytic activity of ricin may be a direct consequence of its ability to fragment DNA and induce apoptosis and not of its ability to inhibit protein synthesis. We also observed no immediate increase in Ca2+ concentration when macrophages were treated with ricin indicating that ricin-induced apoptosis may not involve the activation of a Ca2+ dependent endonuclease(s).

Animals↗

Carbon filament implants promote axonal growth across the transected rat spinal cord.

Significant regeneration of neural pathways following complete transection of the spinal cord has yet to be demonstrated. In the present study, we analyzed the ability of carbon filaments to function as a scaffold for the regrowth of injured axons in the rat spinal cord. Through the use of three different axonal tracing methods, severed spinal axons were observed growing on and between carbon filaments implanted into the completely transected rat spinal cord. Carbon filaments, by providing a favorable adhesive surface and also a possible guiding function, may prove useful in the treatment of spinal cord injury.

Animals↗

Cardiac reactions to two psychological stressors, acting in combination.

56 student volunteers (mean age 21 yr.) participated in a study designed to assess how the Stroop procedure and delayed auditory feedback affect cardiac activity when they are used individually as well as when they are combined in the same task. In a preliminary study, listening to tape-recorded instructions on how to relax produced a significant decrease in cardiac activity. In the major study, when used individually, both the Stroop procedure and delayed auditory feedback produced significant increases in cardiac activity. The largest increase, however, occurred with systolic blood pressure and was induced by delayed auditory feedback. When the Stroop procedure was used in combination with delayed auditory feedback, systolic blood pressure again increased, but this effect was no greater than when delayed auditory feedback was used alone. This pattern of results implies that, when combined, the Stroop procedure and delayed auditory feedback have largely independent effects on cardiac activity and that, when tested under similar conditions, delayed auditory feedback has the larger effect.

Adult↗

Carbon filaments provide support and directionality to growing rat fetal spinal cord explants.

Spinal cord explants obtained from 15 to 17-day-old fetal rats were cultured on bundles of 5-7 microns diameter carbon filaments attached to the bottom of Petri dishes. After a 3 week incubation period, the cultures were fixed and observed by light, scanning, and transmission electron microscopy. Neurites and glial processes were found to be growing both on and between the carbon filaments. The carbon filaments appeared to provide a biocompatible scaffold which promoted adhesion and gave directionality to the growing cell processes. These properties may make carbon filaments a suitable substrate for in vivo implantation into the damaged spinal cord.

Animals↗

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. I. Contraceptive efficacy and side effects. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentre clinical trial, including 19 centres in 13 countries, assessed the contraceptive efficacy and clinical acceptability of a Silastic 382 vaginal ring releasing 20 micrograms of levonorgestrel for at least 90 days. A total of 1005 women entered the study and 8176.74 woman-months of experience was gathered. The rate of intrauterine pregnancy at one year of use was 3.6 per 100 women (95% confidence interval 2.2-5.0), and of ectopic pregnancy, 0.2% (one case). The principal reasons for discontinuation were menstrual disturbances (17.2% at one year), vaginal symptoms (6.0%) and repeated expulsion of the ring (7.1%). The pregnancy rate with this 20 micrograms levonorgestrel-releasing vaginal ring compares favourably with that of a low estrogen combination oral contraceptive tested by WHO and is less than half that of a progestogen-only oral contraceptive in a WHO randomized study. It is concluded that the WHO intravaginal ring releasing an average of 20 micrograms of levonorgestrel per 24 hours is an effective method of contraception for at least one year of use.

Administration, Intravaginal↗

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. II. Expulsions and removals. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between expulsions and removals, and demographic characteristics of 1005 women from 19 centres using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. Emphasis is placed on discontinuations of method use due to expulsions, on the number and rate of expulsions, and the time at which the first expulsion occurred. The overall life-table discontinuation rate due to expulsion was 7.1% at one year. Life-table discontinuation rates increased with parity and were highest in Asian and lowest in European women. In respect to the number of expulsions experienced by women (expulsions did not necessarily lead to discontinuation), the women of high parity and those from Asia and Europe have the highest rates. The life-table first expulsion rate is 29% at one year. Such rates are highest in Chinese and Asian women. Following a first expulsion, the second expulsion rate is 45% by the end of the subsequent six months. The majority of first expulsions occur at defaecation (134 or 57% of 234 women), urination (12%) and during menstruation (17%). Rings were removed by 121 (12%) women on 201 occasions and for a variety of reasons. The main medical reasons were vaginal discharge and irritation, bleeding pain and dyspareunia. Others removed the ring during defaecation, intercourse or because the ring came out of place. Women also removed rings for curiosity, to show their husbands and to clean.

Administration, Intravaginal↗

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. III. The relationship between pregnancy rate and body weight. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

This paper investigates the relationship between pregnancy rates and body weight of 1005 women using a vaginal ring releasing 20 micrograms levonorgestrel per 24 hours. While the overall pregnancy rate at one year was 3.7%, it was found that women have an increasing risk of pregnancy with increasing body weight. For example, a woman of 40 kg has an estimated pregnancy rate of 1.7% in contrast to 9.8% for a woman of 80 kg weight.

Administration, Intravaginal↗

Microdose intravaginal levonorgestrel contraception: a multicentre clinical trial. IV. Bleeding patterns. World Health Organization. Task Force on Long-Acting Systemic Agents for Fertility Regulation.

A multicentred clinical trial was conducted in 12 countries to assess the contraceptive efficacy and side effects of a low-dose levonorgestrel-releasing vaginal ring. Contraceptive efficacy and side effects, expulsions and removals, and the relation between pregnancy rate and admission body weight of the women have been reported previously. The effect of ring use on vaginal bleeding patterns as observed from daily menstrual diaries kept by the women is the object of this paper. A total of 1005 women were fitted with the ring and 702 of them provided a menstrual diary suitable for analysis. The description of the bleeding patterns is made using a 90-day reference period approach and following the guidelines published by WHO. In addition the longest bleeding/spotting episode and longest bleeding/spotting-free interval are calculated over the entire diary length. Half of the ring users have vaginal bleeding patterns similar to normal untreated patterns. A quarter experience irregular bleeding, 10% have prolonged cycles and 10% have shortened cycles. Over one year of continuous use, there appears to be no significant trend in these patterns. Users with the worst bleeding patterns tend to discontinue first during the clinical trial and are influenced by their more recent experience of vaginal bleeding irregularities. Life-table analysis of discontinuation rates gives an underestimation of the true incidence of bleeding irregularities. Some comments are made on the limitations of the methods of analysis of menstrual diaries.

Clinical Trials as Topic↗

Increased blood loss with in situ bypass.

This study uses perioperative hematocrit determinations to quantitatively evaluate blood loss in patients undergoing either in situ (n = 37) or reverse vein technique (n = 44) for femorodistal popliteal or proximal tibial/peroneal reconstruction. The median drop in hematocrit was significantly greater on the fourth postoperative day in the in situ group as compared with the reverse vein group. The median drop in hematocrit was 8.8 +/- 4.2 per cent in the in situ group as compared with 4.8 +/- 4.1 per cent in the reverse vein group (P less than 0.0005). Blood transfusions were required in 11 of 37 patients (30%) in the in situ group as compared with five of 44 patients (11%) in the reverse vein group (P less than 0.05). Despite limitations of a retrospective study, our data indicate that there is greater blood loss with in situ technique as compared with reverse vein technique for femoropopliteal and crural reconstruction.

Aged↗