Plasma concentrations of diazepam and its metabolites after peroral, intramuscular, and rectal administration. Correlation between plasma concentration and sedatory effect of diazepam.

Plasma levels of diazepam, N-demethyldiazepam and free oxazepam were measured gaschromatographically in ten healthy volunteers after 5 mg of diazepam perorally, intramuscularly and rectally (with three different kinds of suppositories). The best absorption of diazepam was found after peroral administration. After an intramuscular injection a delayed absorption with low plasma concentrations of diazepam was found. The basal component of a diazepam suppository seems to have a great effect on the rectal absorption of diazepam. Two of the three different kinds of diazepam suppositories caused higher plasma diazepam concentrations than the intramuscular injection of the drug. There were no great differences in the amount of the metabolites of diazepam after different kinds of administration. The subjective sedatory effect of diazepam lasted approximately as long as the fast distribution of diazepam from plasma took place. A very highly significant correlation between plasma concentration and subjective sedatory effect of diazepam after a single dose was found.     

Comparison of structured observation and pictorial 24 h recall of household activities to measure the prevalence of handwashing with soap in the community

This study compared structured observation with a 24 h pictorial recall of household activities (‘sticker diary’) to measure the prevalence of handwashing with soap (HWWS) in the community. The study was done within a cluster-randomised trial evaluating a handwashing promotion programme in Bihar, India. HWWS at key occasions in mothers and school children was measured by structured observation in 299 households from 32 villages. Sticker diaries recalling common activities, including personal hygiene, were used to measure HWWS in 299 households from a further 20 villages. Sticker diary HWWS prevalence estimates were about 13% points higher than structured observation estimates, but the differences varied by the type of handwashing occasion. This study confirms structured observation as the method of choice for the study of handwashing behaviours. The sticker diary method may be useful in large-scale surveys. Sticker diaries may overestimate HWWS at important occasions, but probably less so than conventional questionnaire tools.     

Bypass circuits as the source of thromboemboli during extracorporeal membrane oxygenation

To determine the presence and extent of thrombus formation in the apparatus used for extracorporeal membrane oxygenation we studied various portions of the polyvinylchloride circuit from five infants who received extracorporeal membrane oxygenation for 70 to 330 hours. All infants had right-sided cannulation. Sections were cut from the circuit at the time of decannulation and subjected to light and scanning electron microscopy. The site that contained the most thrombus formation was the membrane oxygenator bypass circuit, which is subjected to repeated periods of unclamping and clamping to direct blood flow through the membrane oxygenator. Autopsy results from nonsurvivors showed evidence of pulmonary and renal infarcts, a left frontal lobe infarct, a thromboembolus of the left external and internal carotid arteries, and thrombi in the lungs, kidney, brain, and coronary arteries. One survivor had computed tomographic evidence of infarction of the left middle cerebral artery distribution. We suggest that the areas of the extracorporeal membrane oxygenation circuit subjected to repeated changes in flow dynamics may be the source of microemboli.     

Importance of the interaction of midazolam and cimetidine

Six healthy volunteers were given in an open study 15 mg of midazolam orally, and a couple of weeks later the same treatment preceded by 400 mg of cimetidine orally. We followed midazolam serum concentrations and the following pharmacodynamic parameters for five hours: subjective sedation, Maddox wing readings, critical flicker fusion frequency and peak velocity of saccadic eye movements. A statistically significant change was found in Cmax and total AUC between the two sessions. The pharmacodynamic responses differed also clearly from each other suggesting a significant change in midazolam effect even after a single oral dose of cimetidine.     

Perinatal risk assessment for patent ductus arteriosus in premature infants

Data from 2107 inborn premature infants monitored for hemodynamically significant patent ductus arteriosus were used to develop means for clinically assessing at birth the risk of developing patent ductus arteriosus during the first 30 days of life. The overall 30-day incidence rates in birth weight categories 500 to 999, 1000 to 1499 g, and 1500 to 1750 g were 41, 17, and 7%, respectively. At-birth risk estimates obtainable from the derived multivariate functions ranged from 0 to 78% for the 500 to 999 and 1000- to 1499-g categories, and from 0 to 20% for the 1500- to 1750-g category. The derived risk functions provide for enhanced selectivity in the application of measures for the prevention of patent ductus arteriosus.     

Dexmedetomidine premedication for minor gynecologic surgery

The effects of four different doses (0.167, 0.33, 0.67, and 1.0 microgram/kg) of dexmedetomidine, a novel alpha 2-adrenoceptor agonist, on anesthetic requirements, hemodynamics, and plasma catecholamine levels were investigated in a single-blind fashion in 20 healthy (ASA physical status I) women scheduled for uterine dilatation and curettage. The drug was administered intravenously 15 min before anesthesia induction with thiopental. Nitrous oxide/oxygen (70%/30%) was used for maintenance. Dexmedetomidine was well tolerated, and no serious drug-related subjective side effects or adverse events were observed. The most prominent subjective effects were tiredness and decreased salivation. The total amount of thiopental needed to perform uterine dilatation and curettage was decreased dose-dependently from 400 +/- 166 mg (mean +/- SD) after 0.167 microgram/kg of dexmedetomidine to 180 +/- 65 mg after 1.0 micrograms/kg of dexmedetomidine (P = 0.028). Blood pressure, heart rate, and plasma norepinephrine levels were reduced after dexmedetomidine. The optimal dose of dexmedetomidine for single-dose intravenous premedication studies in minor surgery appears to be in the range of 0.33-0.67 micrograms/kg.     

Effects of vitamin C on dark circles of the lower eyelids: quantitative evaluation using image analysis and echogram

Background/aims: The pathogenesis of dark circles of the lower eyelid (DCLE) has been considered to involve stasis and hyperpigmentation of the eyelids. We have already reported that dermal thickness of lower eyelid skin may represent another factor that affects the appearance of DCLE. The aim of this study was to evaluate the efficacy of vitamin C, which is known to increase collagen, on DCLE through a clinical trial.
Methods: Fourteen subjects with DCLE applied either 10% sodium ascorbate (ANa) or ascorbic acid glucoside (AG) lotion in split-face fashion (opposite side: vehicle only) for 6 months. Melanin index (MI), erythema index (EI), thickness and echogenicity of the dermis at bilateral lower eyelids was measured during this trial.
Results: Change in EI was significantly smaller on the ANa-treated side than on the vehicle-treated side. Dermal thickness tended to be thicker for the ANa-treated side than for the vehicle-treated side, although no significant difference was seen. Both EI and dermal thickness tended to change in parallel manner. On the other hand, no significant differences in changes of EI, MI, and dermal thickness were found between AG- and vehicle-treated sides.
Conclusion: ANa may improve DCLE by thickening the eyelid dermis and concealing dark coloration due to congested blood.     

Recent experience with diaphragmatic hernia and ECMO.

In the past 4 years at the Medical College of Georgia, a total of 74 patients underwent extracorporeal membrane oxygenation (ECMO) with 62 (84%) survivors. Forty-seven of these infants had meconium aspiration syndrome and 11 had diaphragmatic hernia. The use of ECMO, when indicated, after reduction and repair of the diaphragmatic hernia, results in normal oxygen delivery, allows time for pulmonary maturation, and increases survival. A total of 27 referrals for diaphragmatic hernia were studied. Six infants had surgical repair and did not require ECMO. Eleven patients, after surgical repair, were treated with ECMO and seven survived. More importantly 10 patients died before the use of ECMO. Six infants died either before or during transport from referring hospitals and four died while in the delivery room or neonatal unit before ECMO. Of these 10 infants, eight were potential candidates for ECMO. Thirteen of the twenty-seven (48%) infants survived. Seven of eleven (64%) infants who received the benefit of ECMO survived. Eight infants who met the criteria for ECMO died before its use. Had ECMO been used in those eight infants, our data suggests that at least four may have survived. The data from this report support the concept that infants undergoing surgical repair of diaphragmatic hernia, when ECMO is not available, should be referred to an ECMO center in the early postoperative period. Furthermore infants with prenatal diagnosis of diaphragmatic hernia should be delivered at a center where surgical as well as ECMO expertise are available.     

Melanin and facial skin fluorescence as markers of yellowish discoloration with aging

Background: Although one clinical sign of aging and/or photoaging is a yellowish discoloration of the facial skin, little is known about the cause of this change. In addition to the increase in the epidermal melanin content, it has been suggested that advanced glycation end products (AGEs), which are known to accumulate in photoaged skin, may affect this discoloration. Aim: The objective of this pilot study was to non‐invasively investigate the roles of melanin and AGEs in this yellowish discoloration of the facial skin. Methods: We examined the spectral reflectance at the cheek in 40 healthy Japanese women of various ages (mean age, 38.1 years) using a reflectance spectrophotometer and a spectrofluorimeter. The degree of yellowish tint was evaluated in terms of b^*. The amount of melanin in the skin was evaluated by calculating the melanin index (MI) A₆₄₀–A₆₇₀ [A_λ: log₁₀ (1/reflectance) at a wavelength of λ]. The amount of AGEs was roughly evaluated using the AGEs index, which is thought to linearly correlate with the amount of intrinsic fluorescence markers irrespective of the concentration of melanin and is defined as follows: AGEs index=I₅/SQR (I₁×I₂). In this equation, the intensities of reflectance are I₁ at an excitation wavelength of 335 nm, I₂ at an emission wavelength of 390 nm and I₅ at 390 nm under an excitation wavelength of 335 nm. Results: Both b^* and the AGEs index were significantly correlated with subject age (r=0.34, P<0.05 and r=0.68, P<0.0001, respectively). Significant correlations were also observed between MI and b^* (r=0.63, P<0.0001) and between the AGEs index and b^* (r=0.53, P<0.0005). However, no significant correlations were seen between MI and the AGEs index. Conclusion: The AGEs index does not appear to be influenced by the amount of melanin and may be utilized as an indicator of the amount of AGEs in the skin. AGEs are likely to play a role in the yellowish discoloration of skin with aging.     

Clinical features of prostate cancer patients younger than 50 years: Report of seven cases

BACKGROUND: The incidence of prostate cancer increases with age and latent cancer is common in older men. But clinical prostate cancer is rare in men aged < 50 years. METHODS: Between 1988 and 2000, we studied seven cases of prostate cancer in men aged under 50 years. The clinicopathological results included: the first sign or symptom; prostate-specific antigen (PSA) at the time of diagnosis; existence of abnormal digital rectal examination (DRE); the differentiation of the cancer and Gleason score; and the outcome of treatment. RESULTS: Six cases were diagnosed as stage D2. One case was diagnosed as stage B2 and the patient underwent radical prostatectomy. None of the cases were detected by mass screening. The PSA at diagnosis was < 10 ng/mL in only one case and that patient underwent radical prostatectomy. Six cases were diagnosed pathologically as poorly differentiated adenocarcinoma. The only patient who survived more than 5 years underwent radical prostatectomy. CONCLUSION: Six of seven cases of prostate cancer were detected at advanced stage. Only one case was thought to be curable and this patient's cancer was detected by chance occult blood test. Because young prostate cancer patients are potential candidates for radical prostatectomy and the sensitivity of PSA might be higher in young men, high-risk groups could be screened by PSA.