Tuberculosis control in South Africa--time for a new paradigm?
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Humans↗
Biomedical subjects
P Graf
Publications and source records attributed to P Graf.
Long-term use of oxy- and xylometazoline nasal sprays induces rebound swelling, tolerance, and nasal hyperreactivity.
It has been suggested but never confirmed, that the severity of the rebound swelling and rhinitis medicamentosa are directly proportional to the period during which the drug is used, to the frequency of its use, and to the amount of drug administered. However, no studies have been performed to evaluate the effects of various amounts of the vasoconstrictors on the development of rhinitis medicamentosa. Moreover, no in vivo studies have yet been performed to investigate whether benzalkonium chloride in nasal decongestant solutions affects the development of rhinitis medicamentosa. This study shows that rhinitis medicamentosa is a condition of nasal hyperreactivity, mucosal swelling and tolerance induced, or aggravated, by the overuse of topical vasoconstrictors with or without a preservative.
Administration, Intranasal↗
[Comment on the contribution: 202 toe transplants to the hand].
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Adult↗
Nonverbal Local Context Cues Explicit but Not Implicit Memory
Memory research distinguishes two components of episodes-the event or item and the spatial-temporal setting or context in which it occurred. The word context is used either globally to denote the physical, social, or emotional environment at study and test or it is used locally to refer to another word or picture that was paired with a particular target. In this article, we report four experiments that investigated the influence of two different nonverbal local contexts on explicit word recognition and implicit word identification test performance. In each experiment, university students studied words that were displayed against various extra-item local contexts, and the contexts were either the same or different at study and test. What differed across experiments was the nature of the contexts: for Experiments 1 and 2, it was a band of color that stretched across the computer screen, and for Experiments 3 and 4, the context was a colored line drawing. The combined findings from all experiments provide no evidence of memory context effects (MCE) on priming. By contrast, recognition test performance showed reliable MCEs but only when the local context was a concrete drawing or when it was a color that was target-related or appropriate. The discussion compared these findings with those from previous studies that concerned the cueing effectiveness of verbal and nonverbal extra-item contexts.
Journal Article↗
Analytical procedure for the determination of the new antitumour drug N-benzoylstaurosporine and three potential metabolites in human plasma by reversed-phase high-performance liquid chromatography.
The staurosporine derivative, N-benzoylstaurosporine (CGP 41 251; I), is a protein kinase C inhibitor that has been selected for phase I clinical evaluation in cancer patients. We have developed a selective and sensitive assay of the drug and three potential metabolites in human plasma. The method is based on reversed-phase high-performance liquid chromatography with fluorescence detection. The sample pretreatment involves liquid-liquid extraction with diisopropyl ether with recoveries over 88%. The limit of detection and limit of quantitation of the parent compound and two metabolites were 0.5 and 1.0 ng/ml, respectively. For the third metabolite the limit of detection and limit of quantitation were 1.0 and 2.0 ng/ml, respectively. Linear calibration lines were obtained over the range of 1-1000 ng/ml. The between-day and within-day precisions were < 7.1% for all the analytes. In plasma the compounds were stable for at least one month if stored at -30 degrees C or below. The applicability of the method for in vivo studies has been demonstrated in a pharmacokinetic study in rat receiving 0.5 mg/kg of the drug as an intravenous bolus injection. Compound I and two metabolites were detected.
Alkaloids↗
Revascularisation versus reconstruction of degloving injuries of the heel: case report.
The anatomy of heel vascularization implies that there is a high risk of necrosis if degloved soft tissue is only sutured back to its former position. Two patients who had sustained similar degloving injuries of the heel are presented. One of them was treated by primary revascularization and the other by secondary reconstruction with a dorsalis pedis flap. The postoperative outcome was investigated to show the value of the salvage operation. Dynamic pressure distribution gait analysis was performed barefoot and in the shoe to investigate postoperative weightbearing on the reconstructed areas. In contrast to the heel reconstruction with the dorsalis pedis flap, the revascularized original heel was stable without development of soft tissue lesions. The salvaged original heel tissue enabled a physiologic pressure distribution beneath the heel and a more physiological rollover process of the foot, comparable to the contralateral foot. In degloving injuries of the heel, revascularization of the soft tissue should be considered whenever possible.
Adolescent↗
Color- and picture-word Stroop tests: performance changes in old age.
The Stroop test comes in different variations, but all of them index performance on a basic task, like color or picture naming, when it is carried out by itself versus when it is performed in the presence of conflicting or incongruent stimuli. The present study examined the hypothesis that Stroop interference--the cost of performing one task in the presence of another--is a general as opposed to a test-specific index of cognitive flexibility. A second goal was to examine changes in Stroop test performance in old age. A group of 129 healthy older adults (> or = 65 years of age) were assessed on the color- and picture-word Stroop test, as well as on a battery of neuropsychological tests. Subjects' performance on each card of both Stroop tests, and various derived (differences and ratios) scores, were used to prepare age-group norms. The use of the norms is illustrated with findings from previous studies. Regression analyses showed age-changes in several aspects of Stroop test performance. Hierarchical multiple regression analyses, and causal modeling showed an age effect on Stroop interference only on the picture-word test but not on the color-word test. Exploratory factor analysis of the Stroop data and the neuropsychological test data revealed different factor loadings for the color- and picture-word test. The combined findings suggest that the color- and picture-word Stroop test measure different cognitive functions, at least in old age.
Aged↗
Benzalkonium chloride in a decongestant nasal spray aggravates rhinitis medicamentosa in healthy volunteers.
A randomized double-blind parallel study with 20 healthy volunteers was performed to research the effect of a preservative in a decongestant nasal spray on the development of rhinitis medicamentosa. Ten subjects received oxymetazoline nasal spray with benzalkonium chloride and the others used oxymetazoline nasal spray without the preservative three times daily for 30 days. Before starting the course of treatment and after its conclusion, recordings of the mucosal surface positions were made with rhinostereometry followed by histamine challenge tests. Symptoms of nasal stuffiness were estimated on visual analogue scales (0-100) in the morning and the evening just before using the nasal spray. After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray with benzalkonium chloride the mean rebound swelling was 1.1 mm and the estimated mean evening symptom score for nasal stuffiness was 43. In the group without benzalkonium chloride the corresponding variables were significantly less marked, with a mean rebound swelling of 0.5 mm (P < 0.05) and a mean evening symptom score of 25 (P < 0.05). The increase in histamine sensitivity in both groups was interpreted as a sign of nasal hyperreactivity. A new type of nasal spray bottle was used that has been shown to prevent bacterial contamination. In conclusion, the long-term use of benzalkonium chloride in oxymetazoline nasal spray accentuates the severity of rhinitis medicamentosa in healthy volunteers.
Administration, Intranasal↗
Benzalkonium chloride in nasal decongestive sprays has a long-lasting adverse effect on the nasal mucosa of healthy volunteers.
Twenty healthy volunteers participated in the present study on the long-term effects of a nasal decongestive spray composed of either a combination of oxymetazoline nasal spray and benzalkonium chloride or of oxymetazoline nasal spray alone. Three months before the present study the participants had undergone treatment with nasal decongestants for 4 weeks. Ten of the subjects had been treated with oxymetazoline nasal spray without benzalkonium chloride and 10 of them had been treated with oxymetazoline nasal spray with benzalkonium chloride. In a double-blind study the subjects who had been treated with oxymetazoline nasal spray and benzalkonium chloride were again treated with the same combination of substances as before, and the subjects who had been treated with oxymetazoline nasal spray alone were also treated again with oxymetazoline nasal spray alone, but on this occasion only for 10 days. Three variables were studied before and after the 10 days of treatment, i.e. nasal mucosa congestion, nasal reactivity and symptom scores. It was found that only the subjects who were treated with the combination of oxymetazoline nasal spray and benzalkonium chloride had increased nasal stuffiness, estimated by symptom scores and measurements of nasal mucosa swelling after 10 days of treatment. It is concluded that a nasal decongestant spray composed of a combination of vasoactive substance and benzalkonium chloride has a long-term adverse effect on the nasal mucosa.
Administration, Intranasal↗
The pathophysiology and treatment of rhinitis medicamentosa.
To evaluate the treatment of rhinitis medicamentosa, 10 consecutive patients discontinued their use of topical vasoconstrictors and were treated with budesonide nasal spray, 400 micrograms, daily for 6 weeks. The thickness of the nasal mucosa, the decongestive effect of oxymetazoline and the histamine sensitivity were measured with rhinostereometry. All patients were able to stop using the vasoconstrictors and objective variables showed that they needed treatment for at least 6 weeks. The results strongly support the theory that the rebound swelling is due to interstitial oedema rather than to vasodilatation. The presence of tachyphylaxis reflected by a reduction in both the decongestive effect of oxymetazoline and a reduction of drug duration was seen.
Administration, Topical↗
Four-week use of oxymetazoline nasal spray (Nezeril) once daily at night induces rebound swelling and nasal hyperreactivity.
A randomized double-blind parallel study with 20 healthy volunteers was performed to examine the effect of oxymetazoline nasal spray on the development of rhinitis medicamentosa. For 30 days, 10 subjects were given oxymetazoline nasal spray once daily at night and placebo in the morning and at noon, while the others used oxymetazoline nasal spray three times daily. Before and after the course of treatment, the mucosal surface positions were determined with rhinostereometry, followed by histamine challenge tests. In the morning and the evening just before use of the nasal spray, symptoms of nasal stuffiness were evaluated on visual analogue scales (0-100). After 30 days, rebound swelling and nasal stuffiness were found in both groups. In the group receiving oxymetazoline nasal spray once daily at night, the mean rebound swelling was 0.8 mm (p < 0.01) and the estimated mean symptom score for nasal stuffiness in the evening was 43 (p < 0.05). In the group receiving the same nasal spray three times daily, the mean rebound swelling was 1.1 mm (p < 0.01) and the mean evening symptom score was 43 (p < 0.05). The finding of an increase in histamine sensitivity in both groups was taken to indicate nasal hyperreactivity. There was no significant difference in the investigated variables between the two groups. It is concluded that the risk of developing rebound swelling and nasal hyperreactivity remains, whether oxymetazoline nasal spray is used once or three times a day for 30 days.
Administration, Intranasal↗
Sustained use of xylometazoline nasal spray shortens the decongestive response and induces rebound swelling.
Long-term use of topical vasoconstrictors for the nose may result in rhinitis medicamentosa, drug addiction and tachyphylaxis. Some authors also believe that the severity of rebound swelling is proportional to the period during which the drug has been used, the frequency of its administration, and the amount of drug given. It has previously been reported that four-week use of the recommended dose of oxymetazoline induces rebound swelling, a sign of rhinitis medicamentosa. To study the effect of an increased amount of vasoconstrictor on rebound swelling and the decongestive effect of the drug, nine healthy subjects were given xylometazoline nasal spray in double the recommended dose (1.0 mg/ml; 0.28 ml in each nostril thrice daily) for 30 days. After 30 days on xylometazoline, the decongestive effect was the same 1 h after drug administration as before starting the medication. Similarly, after 30 days on xylometazoline, the decongestive effect was less 5 h after drug administration than it was 6 h after drug administration at the start of medication (p < 0.005). After 10 days no rebound swelling was recorded, but after 30 days rebound swelling occurred in eight out of nine subjects (p < 0.05). When comparing the results of this trial with the corresponding results of the oxymetazoline study, no further increase in rebound swelling was found. We conclude that long-term use of xylometazoline nasal spray shortens the decongestive response in healthy volunteers. Moreover, double the recommended dose of xylometazoline did not further increase the rebound swelling seen when using the recommended dose of oxymetazoline.
Adolescent↗
Histamine sensitivity in the nasal mucosa during four-week use of oxymetazoline.
In order to objectively study the histamine sensitivity of the nasal mucosa during 30 days of regular use of oxymetazoline nasal spray (0.5 mg/ml; 0.1 ml in each nostril, thrice daily), eight healthy volunteers were examined with rhinostereometry. After 10 days on being treated, the histamine sensitivity was slightly enhanced. After a further 20 days the sensitivity was significantly increased compared to that before the start of the medication (p < 0.05). This increase in histamine sensitivity for the group is significantly greater than that of healthy drug-free volunteers, and the level is comparable with that of patients with non-allergic nasal hyperreactivity (NANH). It is concluded that a hyperreactive mucosal reaction develops after a relatively short time on oxymetazoline and that the results of this study are in line with the recommendation that the drug should not be used for more than 10 days.
Administration, Intranasal↗
[Degloving injuries of the soft tissues of the heel. An indication for microvascular revascularization!].
The sole of the foot has a unique soft tissue structure which allows weightbearing. There is no adequate reconstructive method for soft tissue defects of the weightbearing sole. Soft tissue reconstructions in this area frequently develop stress lesions. After degloving injuries of the heel, the unique vascularisation of the sole may lead to ischemia and consecutive soft tissue necrosis. Revascularisation of degloved heel pads e.g. by reconstruction of the medial calcaneal branch of the posterior tibial artery is recommended as a salvage procedure. In the primary treatment of extremity injuries with severe soft tissue damage a plastic surgeon should be involved.
Adult↗
[Second toe transplantation in loss of a long finger. Indications--planning--technique].
Transplantation of the second toe is a routinely employed method in reconstructive hand surgery. Most often it is used for thumb or midhand amputations. Following partial amputations of digits distal to the MP-joints, toe transplantations are less frequently employed. However, function as well as cosmesis of the hand after partial amputation of digits can considerably be improved by toe transplantation. The length of the reconstructed finger is a most important aspect of operative planning which has influence on operative technique as well as functional and aesthetic results. A smooth junction at the base of the transplanted toe should be maintained. This can be achieved by adequate soft-tissue reduction and exclusion of the metatarsophalangeal joint. Anastomoses of the subcutaneous venous and plantar as well as dorsal arterial vascular systems are recommended.
Amputation, Traumatic↗
Treatment of post-replantation retardation of bone growth by callus distraction. A report of two cases.
Hand and forearm replantation in children may lead to premature closure of the distal radial or ulnar growth-plates. Following successful replantation, bone growth may be retarded, resulting in a length discrepancy between the radius and ulna with secondary deviation of the replanted hand. We present two cases in which callus distraction was employed to correct a length discrepancy. The relative merits of the various treatment options are discussed.
Amputation, Traumatic↗
Episodic spatial memory in adulthood.
Two experiments examined age-related differences in memory for spatial location information in a museum exhibit (Experiment 1) and in a secretarial office (Experiment 2). In Experiment 1, subjects were the visitors to the exhibit (N = 302, 15-74 years of age), and memory was assessed using a map test. In Experiment 2, subjects were 64 young adults (M = 21.2 years) and 32 older adults (M = 71.2 years), and memory was assessed using both a map test and a relocation test. The relocation test required subjects to replace the to-be-remembered targets where they appeared at study. Experiment 1 showed an age-related decline in spatial memory performance, and it placed the onset of this decline in the sixth decade of life. Experiment 2 showed an age-related decline on both tests, but age effects were smaller on the relocation test than on the map test, and when subjects knew that spatial memory would be tested than when they were not informed.
Adolescent↗
Clinical pharmacology of intravenously administered recombinant desulfatohirudin (CGP 39393) in healthy volunteers.
Clinical pharmacology of the intravenously administered recombinant desulfatohirudin CGP 39393 was investigated in 47 healthy volunteers in a multicenter study. Mean peak concentrations after bolus injections of 0.1, 0.3, 0.5, and 1.0 mg/kg were 154, 443, 764, and 1,691 nmol/L, respectively. Intravenous infusions of 0.1 mg/kg/h for 6 h and of 0.2 and 0.3 mg/kg/h for 6 h and 72 h resulted in mean steady-state levels of 78, 227, and 312 nmol/L. Elimination was multiexponential and dose independent. Concordant pharmacokinetic parameters were obtained from both i.v. bolus and infusion experiments (overall average total plasma clearance, 2.20 ml/min/kg; mean residence time, 2.12 h; volume at steady state, 0.27 L/kg). Thrombin inhibition by CGP 39393 was demonstrated ex vivo by the thrombin chromogenic assay (TCA), by activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Following a parabolic function APTT doubled and quadrupled at CGP 39393 concentrations of 100 and 1,000 nmol/L, respectively. Whereas TTs (bovine thrombin 3 or 6 IU/ml) were very sensitive to low CGP 39393 levels with unmeasurable clotting times at CGP 39393 concentrations greater than 30 and 60 nmol/L, PT was prolonged by a factor of only 1.3 above baseline at 300 nmol/L. APTT appears to be most suitable for monitoring the anticoagulant effect of CGP 39393 over a broad concentration range. The drug was well tolerated without clinically relevant bleeding episodes or other adverse events.
Adult↗