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C D Cook

Publications and source records attributed to C D Cook.

At least 19 recordsLinked to original sources

Sex-related differences in the antinociceptive effects of opioids: importance of rat genotype, nociceptive stimulus intensity, and efficacy at the mu opioid receptor.

RATIONALE: Recent studies indicate that morphine is more potent as an antinociceptive agent in male than female rodents and monkeys. OBJECTIVES: To evaluate the influence of sex, nociceptive stimulus intensity and an opioid's relative efficacy on opioid-induced antinociception in rat strains (F344 and Lewis) that display differential sensitivity to morphine antinociception. METHODS: Antinociceptive testing was conducted using a rat warm-water (50-56 degrees C) tail-withdrawal procedure. Dose-response and time-course determinations were performed with various opioids. RESULTS: Across the nociceptive stimulus intensities tested, the high-efficacy mu opioids morphine, etorphine, and levorphanol were equally effective in males and females, but on average 2.5-fold more potent in males. At moderate stimulus intensities, the low-efficacy mu opioid buprenorphine was approximately 0.4-fold more potent in males, and at higher stimulus intensities more potent and effective (greater maximal effect) in males. At low stimulus intensities, the low-efficacy mu opioid dezocine and the mu/kappa opioid butorphanol were greater than 8.9-fold more potent in males, and at moderate stimulus intensities were more potent and effective in males. At a low stimulus intensity, the mu/kappa opioid nalbuphine was more potent and effective in males. At stimulus intensities in which buprenorphine, dezocine, butorphanol, and nalbuphine produced maximal effects in males but not females, these opioids antagonized the effects of morphine in females. Genotype-related differences were noted as opioids were generally more potent in F344 than Lewis males, whereas no consistent differences were observed between F344 and Lewis females. CONCLUSIONS: That sex differences in the potency and effectiveness of opioids increased with decreases in the opioid's relative efficacy and with increases in the nociceptive stimulus intensity suggests that the relative efficacy of mu opioids as antinociceptive agents is greater in male than female rats.

Analgesics, Opioid↗

Modulatory effects of dopamine D3/2 agonists on kappa opioid-induced antinociception and diuresis in the rat.

RATIONALE: The dopamine (DA) D3/2 agonist 7-OH-DPAT has been shown to attenuate the behavioral effects of the mu agonist morphine as well as the development of morphine tolerance. OBJECTIVES: To evaluate the effects of DA D3/2 agonists [7-OH-DPAT, (+)-PD128,907, quinelorane, (-)-quinpirole], a D1 agonist (SKF38393), a D1 antagonist [(+)-SCH23390], a DA antagonist (spiperone), and an indirect DA agonist (cocaine) on the antinociceptive effects of kappa agonists (spiradoline, U69,593, bremazocine) as well as the effects of D3/2 agonists on the diuretic effects of spiradoline. METHODS: Antinociception was determined using a warm water (50-55 degrees C) tail-withdrawal procedure and urine output was collected over a 2-h interval. RESULTS: The antinociceptive effects produced by the kappa agonists varied with the intensity of the nociceptive stimulus (water), as maximal or near maximal effects were obtained with spiradoline at 55 degrees C, U69,593 at 52 degrees C, and bremazocine at 50 degrees C water. 7-OH-DPAT produced a dose-dependent attenuation of the antinociceptive effects of spiradoline, U69,593, and bremazocine. Spiperone completely reversed the effects of 7-OH-DPAT on spiradoline antinociception. (+)-PD128,907 and quinelorane, but not (-)-quinpirole or the other DAergic agents examined, attenuated the antinociceptive effects of spiradoline in a dose- and time-dependent manner. The diuretic effects of spiradoline were attenuated by 7-OH-DPAT, (+)-PD128,907, quinelorane, and (-)-quinpirole, and this attenuation was reversed by spiperone. CONCLUSIONS: The present study demonstrated that some D3/2 agonists can modulate both the antinociceptive and diuretic effects of kappa agonists. These modulatory actions are similar to those obtained against the effects of mu agonists.

Analgesics, Opioid↗

The dopamine D3/2 agonist 7-OH-DPAT attenuates the development of morphine tolerance but not physical dependence in rats.

RATIONALE: The dopamine (DA) D3/2 agonist 7-OH-DPAT attenuates the acute antinociceptive, discriminative stimulus, locomotor activating, and reinforcing effects of mu agonists (for example, morphine). OBJECTIVES: To examine the ability of 7-OH-DPAT to modulate the development of morphine tolerance and physical dependence in the rat. METHODS: Morphine antinociception was assessed using a warm water tail-withdrawal procedure before and following chronic treatment with morphine (15 mg/kg)/7-OH-DPAT (0.3-3.0 mg/kg). Physical dependence was assessed following naloxone-precipitated (1.0 mg/kg) withdrawal in rats treated chronically with morphine (15 and 7.5 mg/kg)/7-OH-DPAT (1.0-10 mg/kg). RESULTS: 7-OH-DPAT attenuated the antinociceptive effects of morphine in both morphine naive and tolerant rats. Additionally, morphine tolerance was attenuated by the coadministration of 7-OH-DPAT in a dose- and time-dependent manner. The magnitude of the attenuation obtained when morphine and 7-OH-DPAT were administered at the same time was similar to that obtained when administration of these drugs was separated by 6 h, indicating that 7-OH-DPAT did not alter morphine pharmacokinetics. In rats rendered tolerant to morphine, the subsequent coadministration of morphine/7-OH-DPAT failed to reverse morphine tolerance, but did attenuate its further development. The level of physical dependence (number and frequency of withdrawal signs) was greater in rats treated with 15 than 7.5 mg/kg morphine. Under both treatment conditions, physical dependence was not altered by 7-OH-DPAT. In morphine-dependent (15 mg/kg) rats, 7-OH-DPAT (3.0 and 10 mg/kg) failed to precipitate withdrawal. CONCLUSION: The D3/2 agonist 7-OH-DPAT can attenuate the antinociceptive effects of morphine in both acute and chronic preparations as well as the development of morphine tolerance. 7-OH-DPAT does not, however, alter morphine physical dependence.

Animals↗

Selective attenuation of the antinociceptive effects of mu opioids by the putative dopamine D3 agonist 7-OH-DPAT.

RATIONALE: The purpose of the present investigation was to evaluate the effects of the D3 agonist (+/-)-7-hydroxy-dipropylaminotetralin (7-OH-DPAT), various dopamine (DA) agonists and DA antagonists on the antinociceptive effects of mu opioids. METHODS: Antinociception was assessed using a warm-water tail-withdrawal procedure in rats. RESULTS: The mu opioids morphine (0.3-10 mg/kg) and dezocine (0.03-3.0 mg/kg) produced dose-dependent increases in antinociception with maximal effects obtained at the higher doses tested. Pretreatment with the putative D3 agonist 7-OH-DPAT (1.0-10 mg/kg) produced a dose-dependent attenuation of the antinociceptive effects of morphine and dezocine. At the highest dose of 7-OH-DPAT tested, the morphine dose-effect curve was shifted rightward by approximately 1.5 log units and the dezocine curve by greater than 2.3 log units. The (+)-isomer of 7-OH-DPAT (1.0 and 3.0 mg/kg) also shifted the morphine dose-effect curve to the right in a dose-dependent manner. The DA D3/D2 agonist (-)-quinpirole (0.1-10mg/kg) attenuated the effects of morphine, but these effects were small in magnitude, not dose-dependent and observed only under a limited set of conditions. The DA D2/D3 antagonist spiperone failed to alter the morphine dose-effect curve, but reversed the effects of 7-OH-DPAT on morphine antinociception. Pretreatment with the DA D1 agonist (+/-)-SKF38393 (1.0 and 10 mg/kg) and the D1 antagonist (+)-SCH23390 (0.1 and 1.0 mg/kg) failed to alter the morphine dose-effect curve. CONCLUSION: The finding that 7-OH-DPAT markedly attenuated the effects of morphine and that these effects were reversed with spiperone suggests that activity at the D3, and possibly the D2, receptor can modulate mu agonist-induced antinociception.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

An examination of the interactions between the antinociceptive effects of morphine and various mu-opioids: the role of intrinsic efficacy and stimulus intensity.

UNLABELLED: We examined the effects of several opioids that vary in intrinsic efficacy at the mu-opioid receptor alone and in combination with morphine in a rat warm water tail withdrawal procedure using 50 degrees C and 52 degrees C water (i.e., low- and high-stimulus intensities). Morphine, levorphanol, dezocine, and buprenorphine produced dose-dependent increases in antinociception using both stimulus intensities. Butorphanol produced maximal levels of antinociception at the low, but not at the high, stimulus intensity, whereas nalbuphine failed to produce antinociception at either stimulus intensity. For cases in which butorphanol and nalbuphine failed to produce antinociception alone, these opioids dose-dependently antagonized the effects of morphine. When levorphanol, dezocine, and buprenorphine were combined with morphine, there was a dose-dependent enhancement of morphine's effects. Similar effects were obtained at the low-stimulus intensity when butorphanol was administered with morphine. In most cases, the effects of these combinations could be predicted by summating the effects of the drugs when administered alone. These results indicate that the level of antinociception produced by an opioid is dependent on the intrinsic efficacy of the drug and the stimulus intensity. Furthermore, the level of antinociception produced by the opioid, not necessarily the opioids' intrinsic efficacy, determines the type of interaction among opioids. IMPLICATIONS: Compared with high-efficacy opioids, lower efficacy opioids produce lower levels of pain relief, especially in situations of moderate to severe pain. When opioids are given in combination, the effects can only be predicted on the basis of the antinociception obtained when the drugs are administered alone.

Analgesics, Opioid↗

Sensitivity to the discriminative stimulus and antinociceptive effects of mu opioids: role of strain of rat, stimulus intensity, and intrinsic efficacy at the mu opioid receptor.

Effects of low (butorphanol, nalbuphine)-, intermediate (buprenorphine)-, and high (morphine, levorphanol)-efficacy mu opioids were examined in F344, Sprague-Dawley (SD), Long-Evans (LE), and Lewis rats using a tail withdrawal and a drug discrimination procedure. In the tail withdrawal procedure using low (50 degrees C), intermediate (52 degrees C), and high (56 degrees C) water temperatures, morphine and levorphanol produced maximal effects in each of the strains and were most potent in F344 and least potent in Lewis. Similar differences across strains were obtained with buprenorphine, and at the high intensity, maximal effects were not obtained in Lewis. At the low intensity, butorphanol produced maximal effects in F344 and SD at relatively low doses, half-maximal effects in LE at very high doses, and no effect in Lewis. Nalbuphine produced near maximal effects in F344 and SD when tested with the low intensity and no effect in the LE and Lewis. Similar results were obtained at the intermediate intensity for these opioids, although the absolute level of antinociception was lower. These results indicate that there are profound differences to the antinociceptive effects of mu opioids across rat strains. The magnitude of these differences increased with higher stimulus intensities and when tested with lower efficacy opioids. In rats trained to discriminate morphine (3.0 or 5.6 mg/kg) from water, there were no consistent differences across rat strains to the effects of these mu opioids. Possible reasons for differences between the results obtained in the tail withdrawal and drug discrimination procedures are discussed.

Analgesics, Opioid↗

Separation of the locomotor stimulant and discriminative stimulus effects of cocaine by its C-2 phenyl ester analog, RTI-15.

During a routine evaluation of several analogs of cocaine, we observed that the C-2 phenyl ester, RTI-15, appeared to suppress motor activity in rats. We subsequently examined RTI-15 for its cocaine-like stimulus effects as well as for its locomotor activity effects. RTI-15 dose-dependently generalized from the cocaine stimulus in rats trained to discriminate 10 mg/kg cocaine from saline with complete substitution (> or = 80% cocaine-lever responding) occurring at 24 mg/kg. During automated locomotor activity tests in mice, cocaine (3-60 mg/kg) dose-dependently increased activity counts and movement time across the entire 1 h test session. RTI-15, however, had little affect on activity counts and movement time from 10-30 mg/kg, and decreased these measures at 60 mg/kg, the highest dose tested. These results indicate that while changing the C-2 methyl ester of cocaine to a C-2 phenyl ester increases dopamine-transporter selectivity, it dissociates its locomotor activity effects from its discriminative stimulus effects suggesting that the underlying mechanisms mediating these effects are not identical.

Animals↗

Dopaminergic activity and the discriminative stimulus effects of mu opioids in pigeons: importance of training dose and attenuation by the D3 agonist (+/-)-7-OH-DPAT.

The present investigation examined the effects of several dopaminergic compounds in pigeons trained to discriminate either a 0.1 (low) or 5.6 (high) mg/kg dose of the mu opioid butorphanol from saline. Various dopamine (DA) re-uptake inhibitors, releasers, a D1 agonist, a D2 agonist and a D3 agonist engendered partial substitution (50-79% butorphanol responding) for the butorphanol stimulus in the low-dose group. In the high-dose group, with a few exceptions, these compounds produced predominately saline responding. In the low-dose group, the opioid antagonist naloxone antagonized the stimulus effects produced by butorphanol, but failed to attenuate the butorphanol-like discriminative stimulus effects produced by the DA re-uptake inhibitors mazindol and cocaine. The D1 antagonist (+)-SCH 23390 and the D2 antagonist raclopride failed to attenuate the stimulus effects produced by either the low or high training dose of butorphanol. Doses of mazindol and cocaine that engendered between 16% and 70% butorphanol responding failed to alter the butorphanol dose-effect curve in either the low- or high-dose group, indicating a less than additive interaction. In the high-dose group, the D3 agonist (+/-)-7-hydroxy-dipropylaminotetralin [(+/-)-7-OH-DPAT] attenuated butorphanol's stimulus effects in a dose-dependent manner along with the butorphanol-like stimulus effects produced by nalbuphine and morphine. The present findings indicate that direct and indirect DA agonists share similar stimulus effects with a low but not high training dose of butorphanol, and in the high-training dose group, activation of the D3 receptor by (+/-)-7-OHDPAT results in the attenuation of the discriminative stimulus effects of mu opioids.

Analgesics, Opioid↗

Is anterior chamber lens implantation after intracapsular cataract extraction safe in rural black patients in Africa? A pilot study in KwaZulu-Natal, South Africa.

PURPOSE: There are an estimated 16 million people blind from cataract world-wide. In many areas the routine operation is intracapsular cataract extraction (ICCE). The role of modern anterior chamber (AC) intraocular lenses (IOLs) is being explored, and they have been shown to be safe and successful in Asia. Are they equally safe in rural black African populations? METHODS: One hundred black patients aged 50 years and over who attended Edendale Hospital were enrolled in a pilot study of insertion of AC IOLs after ICCE. They were followed up for 6 months. RESULTS: With financial remuneration, the follow-up rate at 8 weeks increased from the usual 30% to 72%. At 6 months, 67% of eyes achieved a correlated visual acuity of 6/18 or better. Thirty per cent had persistent uveitis, 16% had peripheral anterior synechiae beyond the points of haptic contact, and 5% had an intraocular pressure greater than 21 mmHg. CONCLUSIONS: A randomised trial comparing ICCE with AC IOL and extracapsular cataract extraction with posterior chamber IOL is probably not justified at this time in this population. However, there may be wide variations in the reaction of the eyes of different African ethnic groups to IOLs. In view of the successful use of AC IOLs in Asian eyes, further pilot studies of AC IOLs may be warranted in other parts of Africa where ICCE is the routine procedure.

Black or African American↗

Delta opioid-like discriminative stimulus effects of mu opioids in pigeons discriminating the delta opioid BW373U86 from saline.

The purpose of this experiment was to examine the substitution patterns produced by opioids with activity at the mu receptor in pigeons trained to discriminate the delta opioid BW373U86 from saline. A low dose of naltrindole (0.1 mg/kg) produced at least a 16-fold rightward shift in the dose-effect curve for the stimulus effects of BW373U86 (yielding a pK(B) = 7.9), whereas a relatively high dose of naloxone (1.0 mg/kg) produced only a 2-fold rightward shift (yielding a pK(B) = 5.6). The delta opioid SNC80 and the mixed mu/kappa opioids ethylketocyclazocine and ketocyclazocine substituted completely for the BW373U86 stimulus. Various opioids with activity at the mu receptor (levallorphan, [-]-cyclazocine, [-]-n-allylnormetazocine, morphine, butorphanol, nalbuphine, [+]-propoxyphene, etorphine, fentanyl) substituted partially for the BW373U86 stimulus. There was no relationship between the substitution patterns produced by these opioids and their relative intrinsic efficacy at the mu receptor, their relative selectivity for the mu receptor or their relative affinity for the delta receptor. Naloxone (1.0 mg/kg) was considerably more effective than naltrindole (0.1 mg/kg) in antagonizing the substitution patterns produced by etorphine, ethylketocyclazocine, ketocyclazocine and butorphanol, suggesting that these effects were not mediated by activity at the delta receptor. There was no evidence that these opioids antagonized the BW373U86 stimulus, suggesting that they were not functioning as low efficacy agonists at the delta receptor. The kappa opioids bremazocine and U50,488, as well as the non-opioids cocaine and pentobarbital, failed to produce appreciable levels of BW373U86 responding. The present findings indicate that in pigeons mu opioids most likely produce delta-like discriminative stimulus effects by activation of mu rather than delta or kappa receptors.

Animals↗

Discriminative stimulus effects of opioids in pigeons trained to discriminate fentanyl, bremazocine and water: evidence of pharmacological selectivity.

The purpose of the present investigation was to examine the discriminative stimulus effects of opioids with activity at mu and kappa opioid receptors, in pigeons trained to discriminate the mu opioid fentanyl, the kappa opioid bremazocine and water in a three-choice discrimination task. The apparent pkB values obtained for naloxone as an antagonist of the stimulus effects of fentanyl were higher than those obtained against the bremazocine stimulus. The mu opioids morphine and l-methadone substituted for the fentanyl stimulus, the kappa opioids U50,488 and U69,593 substituted for the bremazocine stimulus, and the non-opioid pentobarbital failed to substitute for either the fentanyl or bremazocine stimulus. A series of opioids with activity at both the mu and kappa opioid receptor sites, including nalorphine, butorphanol, buprenorphine, nalbuphine, ethylketocyclazocine, (-)-ketocyclazocine, (-)-n-allylnormetazocine (NANM) and levallorphan, produced high levels of substitution for the fentanyl stimulus without producing appreciable levels of substitution for the bremazocine stimulus. At doses that did not substitute for the fentanyl stimulus, (-)-NANM, levallorphan, nalorphine and nalbuphine partially antagonized the bremazocine stimulus (i.e. produced responding on the water key). Butorphanol and buprenorphine also antagonized the bremazocine stimulus, although this effect was evidenced only at doses that substituted for the fentanyl stimulus. In contrast, even when tested up to doses that markedly decreased rates of responding, ethylketocyclazocine and (-)-ketocyclazocine failed to antagonize the bremazocine stimulus. The present findings indicate that in this three-choice task the fentanyl-like substitution patterns produced by opioids with activity at both the mu and kappa opioid receptors are similar to those reported in pigeons trained to discriminate either fentanyl or bremazocine from saline (i.e. two-choice tasks). In this task, however, the level of kappa antagonist activity evidenced by these opioids was considerably less than that obtained in pigeons trained to discriminate bremazocine from saline.

Analgesics↗

Effects of the delta opioid against BW373U86 in pigeons trained to discriminate fentanyl, bremazocine and water in a three-choice drug discrimination procedure.

The delta opioid agonist BW373U86 was examined alone and in combination with mu agonists in pigeons trained to discriminate the mu agonist fentanyl (0.056 mg/kg), the kappa agonist bremazocine (0.017 mg/kg), and distilled water in a three-choice drug discrimination procedure. BW373U86 (0.01-10 mg/kg) produced a dose-dependent increase in fentanyl-appropriate responding and complete generalization to fentanyl in four of five subjects. BW373U86 did not elicit bremazocine-appropriate responding in any of the subjects. Fentanyl-appropriate responding elicited by BW373U86 was antagonized by the delta selective antagonist naltrindole (0.1-10 mg/kg) but not by the mu selective antagonist naloxone (0.1-30.0 mg/kg). When BW373U86 was administered in combination with the mu agonists fentanyl, morphine and nalbuphine, a low dose of BW373U86 (0.01 mg/kg) that elicited primarily water-appropriate responding when administered alone did not produce a significant change in the ED50 values for fentanyl, morphine or nalbuphine. Higher doses of BW373U86 (0.1-1.0 mg/kg) increased levels of fentanyl-appropriate responding elicited by low doses of fentanyl, morphine and nalbuphine to levels similar to those produced by BW373U86 alone. These results indicate that BW373U86 shares discriminative stimulus properties with the mu agonist fentanyl in pigeons, possibly by acting at delta opioid receptors. However, BW373U86 does not potentiate the discriminative stimulus effects of mu agonists or share discriminative stimulus effects with the kappa agonist bremazocine.

Analgesics↗

The expert witness: real issues and suggestions.

Medical malpractice lawsuits generally require expert testimony. Defendants and plaintiffs deserve expert testimony that is exacting, accurate, and consistent. A study of four frequently testifying experts was undertaken with review of depositions, reports, and trial transcripts of those experts. Contradictions in claimed medical principles from one case to the next were found and examples were cited for each expert. The review suggested that expert testimony regarding the standard of care may be neither reliable nor accurate for the purposes of judging physician conduct is lawsuits. Presently, no peer review or sanction process has been implemented to ensure accuracy and reliability of expert testimony used in medical malpractice lawsuits. We recommend changes that would include independent court-appointed experts, central filing of opinion letters by experts with authoritative text citations, and a sanction process by courts and/or authorized boards for testimony that is deemed inaccurate, false, or contradictory to the standard of care.

Expert Testimony↗

Prevalence and incidence of blindness due to age-related cataract in the rural areas of South Africa.

OBJECTIVES: The Bureau for the Prevention of Blindness is responsible for the provision of cataract surgery to the rural indigent population of South Africa. It is important for the Bureau to know both the prevalence and the incidence of cataract blindness in the population. DESIGN, SETTING AND SUBJECTS: Blindness prevalence surveys were conducted in KwaZulu in 1990 and 1993. OUTCOME MEASURES AND RESULTS: The prevalence of cataract blindness was 0.59% (95% confidence interval 0.21) in 1990 and 1993. The prevalence of aphakia was 0.1% in 1990 and 0.2% in 1993, demonstrating a probable increase in the delivery of cataract surgical services, although this had not produced a demonstrable fall in the prevalence of cataract blindness. The calculated annual incidence of cataract blindness was 0.14%. CONCLUSION: Among a rural population of approximately 19 million South Africans, there is a backlog of 113,000 unoperated cataract-blind people and an incidence of 27,000 new cataract blind per year. The implications of this backlog for cataract blindness in our rural areas are discussed.

Age Factors↗

Impact of a sight-saver clinic on the prevalence of blindness in northern KwaZulu.

The prevalence of blindness in the Ingwavuma district of northern KwaZulu was 1% (95% confidence interval 0.75 - 1.25) in 1990, and the prevalence of blindness due solely to age-related cataract was 0.39% (95% CI 0.24 - 0.54). Eight sight-saver clinics were held between 1990 and 1993. Nine hundred and thirteen patients were seen and 113 cataract extractions performed at a cost of R62,000. The prevalence of blindness due solely to age-related cataract was reduced by 25% to 0.29% (95% CI 0.17 - 0.41). The overall prevalence of blindness was reduced by 4% to 0.96% (95% CI 0.72 - 1.20). The provision of aphakic spectacles to aphakic patients whose spectacles have either been lost or broken would effect a further 11% reduction to 0.85% (95% CI 0.63 - 1.07). The establishment of a permanent sight-saver clinic staffed by an ophthalmic medical assistant who is working full-time in this capacity would facilitate an improvement in the delivery of eye care in the area.

Age Factors↗

Prevalence and causes of low vision and blindness in northern KwaZulu.

A survey of the prevalence of blindness and low vision was conducted in the Ingwavuma district of KwaZulu to assess the effectiveness of existing eye care facilities in the prevention and treatment of impaired vision and blindness. One hundred subjects from each of 60 randomly selected clusters (N = 6,090) were screened. Of these, 293 were identified and referred to an ophthalmologist for examination. Of the 268 (91,5%) examined, 241 were found to have visual impairment. Sixty-one of these people were blind, 85 had low vision, 61 were blind in one eye but had normal vision in the other, and 34 had low vision in one eye but normal vision in the other. The prevalence of blindness was 1,0% (95% confidence interval 0,7-1,2%), and the prevalence of impaired vision was 1,4% (95% confidence interval 1,1-1,7%). Age-related cataract (59,0%) and chronic glaucoma (22,9%) were the two main causes of blindness. Age-related cataract (75,3%), refractive error (10,0%) and chronic glaucoma (4,7%) were the main causes of impaired vision. Existing eye care services for the region have reduced the prevalence of blindness by only 7,0%. The training of ophthalmic nurses and the establishment of a sight-saver clinic in the area are necessary to reduce the prevalence of low vision and blindness.

Adolescent↗

Thrombomodulin activity and localization.

An overview on the properties, actions and localization of thrombomodulin (TM) in situations of tissue injury and in selected tumors is presented. The localization and activity of TM after injury to vascular endothelium shows that following balloon catheter denudation of the endothelium of the rabbit aorta, the activity and immunohistochemical staining is markedly reduced. The functional and antigenic levels approach the control levels approximately one week after the initial injury. The results suggest that the neointimal smooth muscle cells express TM. This phenotypic plasticity of the neointimal smooth muscle cells may be important in conferring thrombo-resistance to the lumenal lining cells of vessels after injury. Studies are also reviewed on the use of soluble recombinant TM to prevent thrombosis after ligature of vessels in an experimental model. Further characterization on the immunohistochemical distribution of TM in normal tissues and tumors shows that staining with a monoclonal anti TM antibody can be very useful in separating mesotheliomas from pulmonary adenocarcinomas. These studies may lead to insights concerning the role of TM in tissue-injury-repair and tissue differentiation.

Adenocarcinoma↗