P. Van Der Bijl

A comparative light-microscopic, electron-microscopic and chemical study of human vaginal and buccal epithelium.

The scarcity of sizeable specimens of normal oral mucosa for experimental purposes has hampered research on oral epithelium. Because large specimens of viable human vaginal mucosa are readily available and because vaginal and buccal epithelia are microscopically similar, vaginal mucosa has been used successfully to establish a human cyst model in experimental animals. The ultrastructure and distribution of keratin filaments in these epithelia are also similar, as is their permeability to water and a number of chemical substances. Therefore, if vaginal mucosa could be substituted for buccal mucosa it would expedite research on the epithelium of buccal mucosa. To strengthen further the concept that vaginal epithelium could replace buccal epithelium in certain experimental studies, the thickness of these epithelia, their patterns of surface keratinization, the presence or absence of intercellular lipid lamellae and their lipid contents were now compared. Thirty-three specimens of vaginal mucosa from postmenopausal women and 36 of buccal mucosa were investigated. To compare the thickness of the epithelial layers the number of cell layers in sections of 20 vaginal and 20 buccal mucosal specimens were counted in the three thickest and three thinnest regions of each specimen. Surface keratinization was evaluated on sections stained with the Picro-Mallory method. To demonstrate lipid lamellae two vaginal and two buccal mucosa specimens were examined electron microscopically after normal fixation and postfixation in ruthenium tetroxide. Following solvent extraction of 11 vaginal and 14 buccal epithelia, quantitative lipid analyses were performed using thin-layer chromatography. No statistically significant differences were found between the maximum and minimum number of epithelial cell layers. The patterns of surface keratinization and the distribution and appearance of the lipid lamellae in the intercellular spaces were similar. The lipid composition of the two epithelia corresponded, except for the cholesterol esters and glycosylceramides, which were higher in buccal epithelium. Ceramides for vaginal epithelium and triglycerides for buccal epithelium were not determined. Based on structural similarities, a similar lipid composition and earlier findings, it is concluded that vaginal epithelium can be used as a substitute for buccal epithelium in certain in vitro, and possibly for in vivo, studies.

Preanesthetic medication with rectal midazolam in children undergoing dental extractions

Three different dosages (0.25, 0.35, and 0.45 mg/kg) of rectally administered midazolam were compared with each other and with placebo for preanesthetic medication in children undergoing dental extractions. Eighty patients between the ages of 2 and 10 years were randomly allocated into four groups in this double-blind study. The results from this trial show that 30 minutes after rectal administration of all doses of midazolam, good anxiolysis, sedation, and cooperation were obtained in most patients. A high prevalence (23%) of disinhibition reactions was observed, particularly in the 0.45 mg/kg group. For this reason, 0.25 or 0.35 mg/kg appears to be the dose of choice when rectal midazolam is used for premedication in children.

Rectal ketamine and midazolam for premedication in pediatric dentistry

Rectally administered midazolam (0.30 mg/kg) and ketamine (5 mg/kg) were compared for preanesthetic medication in children undergoing dental extractions. Sixty patients between the ages 2 and 9 years were randomly allocated to three groups in this double-blind study. In one group of patients who received ketamine rectally, intravenous midazolam (0.05 mg/kg) also was administered immediately after induction of anesthesia. The results from this trial show that 30 minutes after rectal administration of the two drugs, good anxiolysis, sedation, and cooperation were obtained in most patients. Although midazolam appeared to be marginally more efficacious than ketamine in the majority of assessments made and seemed to have less adverse effects, no statistically significant differences could be shown. Ketamine showed a slight decrease and midazolam a slight increase in average blood pressures after premedication. These blood pressure differences were, however, considered to be of little clinical importance.

Disinhibitory reactions to benzodiazepines: A review

This article reviews some of the important aspects of benzodiazepine-induced disinhibitory reactions. Although reactions of this type are relatively rare, they may sometimes manifest themselves in aggressive behavior accompanied by suicidal or homicidal tendencies. It appears that these reactions occur more commonly in younger patients, although the elderly (above 65 years) may also be at risk. Many mechanisms have been postulated, but none truly explain how these reactions arise. The concept that central cholinergic mechanisms may play a role, however, remains attractive and stems primarily from physostigmines ability to successfully reverse this type of reaction. The potential role of the benzodiazepine antagonists, eg, flumazenil, in reversing disinhibitory reactions is also discussed. Apart from patients who previously exhibited poor impulse control, there are no reliable indicators for recognizing potential candidates for this type of reaction. To minimize the occurrence of disinhibitory reactions, some guidelines, which include the avoidance of certain drug combinations, the use of low doses of benzodiazepines, slow incremental intravenous administration, and good rapport with patients, are presented.

Cardiac dysrhythmias associated with intravenous lorazepam, diazepam, and midazolam during oral surgery

The incidence and nature of cardiac dysrhythmias occurring during intravenous sedation with lorazepam, diazepam, and midazolam for oral surgery were studied. Sixty American Society of Anesthesiologists (ASA) I patients of both sexes between the ages 17 and 32 years were randomly allocated to three groups. Groups received either intravenous lorazepam (.05 mg/kg), diazepam (.25 mg/kg), or midazolam (.1 mg/kg) prior to the oral surgical procedure. Electrocardiograms were made before medication and thereafter throughout the entire procedure. Of the 60 patients studied, 16 (26.7%) exhibited dysrhythmias during the surgical procedure. If sinus dysrhythmias were excluded as a cause of abnormal rhythms, only six patients (10%) exhibited dysrhythmias during surgery. No atrial or ventricular premature beats were recorded for the lorazepam group. In the diazepam group five of the patients (25%) exhibited dysrhythmias; 15% were mainly unifocal ventricular premature beats. Only one patient in the midazolam group exhibited unifocal ventricular premature beats.

Comparison of various physiologic and psychomotor parameters in patients sedated with intravenous lorazepam, diazepam, or midazolam during oral surgery

Intravenously administered lorazepam (0.05 mg/kg), diazepam (0.25 mg/kg), and midazolam (0.1 mg/kg) were compared for sedation during oral surgery under local anesthesia. Sixty patients were randomly allocated into three groups in this double-blind, parallel study. The results from this trial show that all three drugs provide satisfactory sedation. Average mean arterial pressures, however, decreased significantly with midazolam and diazepam. Statistically significantly higher heart rates during the entire procedure were also found for lorazepam when compared with diazepam and midazolam. At the postblock stage, the midazolam group had respiratory rates that were significantly higher than those of the other two drug groups. Patients in the diazepam and midazolam groups took significantly longer to complete the pegboard test at the preblock stage than those in the lorzepam group. At 1, 1.5, and 2 hours after arrival in the recovery room, an inversion of groups took place, with the lorazepam group taking significantly longer for their tests than the other two groups. Significantly more improvement in anxiety levels was found at 10 minutes postdrug for the patients who had received diazepam and this tended to remain so on arrival in the recovery room. When compared with the other two groups, significantly more patients in the lorazepam group reported giddiness/dizziness and significantly more in the diazepam group reported pain on injection.

Burning mouth syndrome: Evaluation of multiple variables among 85 patients

The relationship between burning mouth syndrome and 48 variables was investigated in 241 patients, 45 years old and older, who had attended the Oral Medicine Clinic of the Faculty of Dentistry, University of Stellenbosch during a period of 4 years. A total of 85 cases of burning mouth syndrome were diagnosed in 65 women and 20 men. Statistically significant relationships (p < 0.05) were found with self-medication, xerostomia, and other salivary disturbances in both men and women with burning mouth syndrome when compared with their respective controls. Among the women with BMS, significant relationships were also found with anemia, inadequate diet, chronic infection, hormone therapy, ulcerative/erosive lesions, and atrophy. In contrast men with BMS showed statistically significant relationships between taking prescribed medication, central nervous system disturbances, gingivitis, and denture-related problems. In addition, significant associations were related to variables such as psychogenic factors, regurgitation, flatulence, and periodontitis.

Permeation of sumatriptan through human vaginal and buccal mucosa.

Continued interest in the various routes by which sumatriptan may be administered prompted us to investigate its passage through buccal mucosa. Because human buccal mucosa is scarce, we proposed using the relatively abundant vaginal mucosa, which has been shown to have comparable diffusion rates for a number of widely varying molecules, as a model of buccal mucosa. In addition, by comparing these two tissues with respect to their permeability to sumatriptan, the human vaginal/buccal mucosa model could be further evaluated. Clinically healthy human vaginal and buccal mucosa specimens were used in the permeability studies. Permeability to sumatriptan was determined using a continuous flow‐through diffusion system in the presence and absence of permeation enhancers. No statistically significant differences in permeability could be demonstrated for both mucosae toward sumatriptan. Flux values obtained in the absence and presence of glycodeoxycholate and lauric acid (1:1 molar ratio) to sumatriptan of buccal and vaginal mucosa, respectively, were not significantly different. The results obtained further support the hypothesis of the vaginal/buccal mucosal in vitro permeability model and suggest that this model may be used in conjunction with various absorption enhancers. Further studies on the buccal route of absorption of sumatriptan are thus warranted.

Fluctuation of the volume of distribution of amikacin and its effect on once-daily dosage and clearance in a seriously ill patient

ObjectiveThe main aim of the trial was to determine the extent to which the volume of distribution of amikacin fluctuates in a seriously ill patient receiving copious quantities of i.v. fluid over an extended term of treatment. The impact of the volume fluctuation on amikacin therapeutic peak concentrations was also assessed.Design and settingThe case report describes a young, previously healthy male adult admitted to the surgical ICU of a teaching hospital following trauma to the head and central nervous system.InterventionThe patient received 1 g of amikacin once-daily i. v. for 35 consecutive days as part of an antimicrobial regimen. Blood samples were drawn for routine amikacin concentration determinations on 14 occasions, extending over the entire term of treatment, from which the required pharmacokinetic parameters were determined.ResultsThe volume of distribution of amikacin varied extensively from 0.27 to 0.61 l/kg (normal range 0.27±0.06 l/kg) notwithstanding the fact that amikacin clearance remained satisfactorily high throughout the term of treatment.ConclusionsOnce-daily therapeutic amikacin concentrations fluctuate extensively and rapidly in the seriously ill patient receiving copious quantities of i.v. fluids, despite competent renal function. The volume expansion seen in our patient is difficult to account for in terms of the extracellular fluid compartment only.Recommendations(a) Once-daily regimen amikacin peak concentrations should be frequently monitored in the seriously ill patients; (b) once-daily amikacin regimens are best monitored using blood specimens drawn at 1 and 6–8 h post administration.

Intravenous midazolam in oral surgery

Intravenously administered midazolam (0.1 mg/kg) was compared with placebo in a randomized study in 50 patients undergoing oral surgical procedures under local anaesthesia. The results obtained from this study showed that midazolam when compared to placebo had slight cardiovascular and respiratory depressant effects, diminished anxiety and caused amnesia. It also provided better operating conditions and possibly stimulated appetite.