Postmenopausal craniofacial hyperhidrosis treated with botulinum toxin type B

Hyperhidrosis can seriously impair patients’ quality of life. Medical history, including heredity and hyperhidrosis during youth, as well as current age and time elapsed since menopause, is important to consider when distinguishing between postmenopausal hyperhidrosis and vasomotor symptoms to enable adequate treatment. This report concerns a subgroup of eight postmenopausal patients participating in a randomized controlled trial regarding botulinum toxin (Btx) type B treatment in craniofacial hyperhidrosis. Even though the sample size is small and the enrolment is not yet completed, the promising data collected hitherto are interesting to present in advance because this subtype of craniofacial hyperhidrosis is often underrecognized and challenging to treat. Patients were randomized to receive Btx type B or placebo. Measurements were performed before treatment and 3 ± 1 weeks after. The Dermatology Life Quality Index (DLQI) score was improved for all patients after Btx type B treatment (n = 3) with a median decrease of 9 points (90% median improvement). The placebo group (n = 5) had a median increase of 2 points (–18% median decline). When the same group (n = 5) received Btx type B (open) the DLQI score decreased with a median of 7 points compared with baseline (91% median improvement). Treatment‐related adverse events were temporary and did not prevent improvement of life quality. Furthermore, background data evaluation uncovered interesting findings regarding vasomotor symptoms in relation to postmenopausal hyperhidrosis. In conclusion, the results indicated that Btx type B seems to be a safe and effective treatment in postmenopausal craniofacial hyperhidrosis. Further research is encouraged.     

Computational modeling to predict effect of treatment schedule on drug delivery to prostate in humans.

PURPOSE: To evaluate a computational approach that incorporates experimental data in preclinical models to depict doxorubicin human tissue pharmacokinetics. EXPERIMENTAL DESIGN: Beagle dogs were given 2 mg/kg doxorubicin as i.v. bolus, 4-h infusion, or 96-h infusion. Concentrations in plasma, prostate (target tissue), heart (toxicity), and major tissues for disposition were determined and modeled. Model parameters were obtained after the bolus injection with model validation based on the 4-h and 96-h infusion data. Clinical pharmacokinetic data and scale-up gave doxorubicin profiles in human prostate and heart. RESULTS: In agreement with in vitro results, tissues were best modeled with two compartments, one rapidly and one slowly equilibrating. The developed tissue distribution model predicted concentrations for all three administration regimens well, with an average deviation of 34% (median, 29%). Interspecies scale-up to humans showed that the change from a bolus injection to a slow, 96-h infusion (a) had different effects on the drug partition and accumulation in heart and prostate, and (b) lowered the peak concentration in the plasma by approximately 100-fold but had relatively little effect on maximal heart concentration ( approximately 33% lower). The simulated drug exposure in a human prostate was above the exposure required to inhibit tumor proliferation but was 30 to 50 times below that needed for cell death. CONCLUSION: The present study shows a computation-based paradigm for translating in vitro and in vivo preclinical data and to estimate and compare the drug delivery and pharmacokinetics in target tissues after different treatment schedules.     

Intraprostatic chemotherapy: distribution and transport mechanisms.

PURPOSE: The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy. EXPERIMENTAL DESIGN: We studied the delivery and spatial distribution of a fluorescent drug, doxorubicin, in the prostate of beagle dogs, after intraprostatic or i.v. administration. Drug concentrations were measured using high-performance liquid chromatography and confocal fluorescence microscopy. RESULTS: I.v. and intraprostatic injections yielded qualitatively and quantitatively different doxorubicin distribution in the prostate. A relatively homogeneous distribution was found after i.v. administration, whereas intraprostatic injection yielded a highly heterogeneous distribution with >10-fold higher concentrations localized in a cone-shaped glandular lobule bound by fibromuscular stroma, compared with other parts of the prostate. Compared with i.v. injection, intraprostatic injection yielded, on average, approximately 100-fold higher tissue-to-plasma concentration ratio, ranging from 963-fold near the injection site to 19-fold in the contralateral half of the prostate. The drug distribution within the prostate further suggests an important role for acinar flow in intraprostatic drug transport. CONCLUSIONS: Intraprostatic administration represents a viable option to deliver high drug concentrations within the prostate. The results further suggest the fibromuscular stroma separating the prostatic lobules as a major barrier to drug transport and convective flow as an important drug transport mechanism in the prostate.     

Verbal learning in Alzheimer's dementia.

Many recent findings in Western countries suggest that episodic recall is the most sensitive discriminator between patients with mild Alzheimer disease (AD) and the normal elderly, while semantic memory tends best to differentiate between moderate and severe AD patients. The present study is the first to examine in detail the episodic memory of Chinese AD patients in Hong Kong with a locally developed list learning test, comparing procedures that do or do not encourage the use of semantic organization. The performance of 28 AD patients was compared to that of 30 normal controls. AD patients did significantly worse in terms of acquisition and retention and also benefited significantly less from external organization cues. In the discriminant function analysis, the rate of forgetting in the random condition and the total retention score in the blocked condition were found to be the best predictors for differentiating between AD patients and controls. On the other hand, in the differentiation between mild and moderate AD, semantic clustering in the blocked condition was found to be the best predictor. Results of the present study were discussed in the light of the previous findings reported in the Western countries and the neuropathological changes of AD patients.     

Parental perception of neonatal intensive care in public sector hospitals in South Africa.

BACKGROUND: Little is known about parental experience and decision making with regard to premature infants requiring intensive care in developing countries. We undertook this study to characterise parents' experience of physician counselling and their role in making life-support decisions for very low-birth-weight (VLBW) (birth weight < 1 501 g) infants born in South Africa's public-sector neonatal intensive care units (NICUs). METHODS: Parents of surviving VLBW infants treated in three Johannesburg-area public hospitals and attending follow-up clinics in August 2001 were interviewed regarding their experience of perinatal counselling on outcomes (pain, survival, disability), perception of actual and optimal decision making, and satisfaction with NICU communication. RESULTS: Parents of 51 infants were interviewed. Seventy-five per cent of parents reported antenatal counselling by physicians on at least one perinatal topic (severe disability, pain, death, finances or religious/moral considerations). The majority of parents (> 60%) who received counselling thought that these topics had been discussed adequately. Most parents reported that doctors had the primary decision-making role, either without consulting them (41%) or after consulting them (37%). Joint decision making was rare (14%). Parents wanted more input in life-support decisions than they reported being given. CONCLUSION: Counselling is not consistently provided in public-sector hospitals in Johannesburg. Parents of premature infants want a larger share in NICU decision making than they currently experience. Most parents were satisfied with communication later during their infant's hospitalisation. South Africa presents a unique opportunity to study the use of advanced medical technologies in a nation with marked disparities in access to care.     

Art in medical education: Especially plastic surgery

The importance of art studies in the training of plastic surgeons has not been well recognized. Presently, very few medical schools offer courses on art or include it in the humanities. Because the study of art is a great experience that helps to develop the trained eye, the inclusion of art in medical education is recommended. For plastic and aesthetic surgeons, art knowledge can greatly add to the development of surgical skill. Courses in drawing, modeling, and casting are recommended along with lectures or seminars on art appreciation.Delivered as the Nojarova Lecture at the New York Academy of Medicine, the New York Regional Society of Plastic and Reconstructive Surgery, March 3, 1990. Also given at the Italian-American Conference of Plastic Surgeons, Venice, Italy, September 23, 1990     

Acetylator genotype-dependent metabolic activation of carcinogenic N-hydroxyarylamines by S-acetyl coenzyme A-dependent enzymes of inbred hamster tissue cytosols: relationship to arylamine N-acetyltransferase

A genetic polymorphism in S-acetyl coenzyme A (AcCoA)-dependentN-acetyltransferase has been associated with a differentialrisk for certain cancers in humans. In this study, several tissuesfrom the inbred Syrian hamster with a genetically defined AcCoA-dependentN-acetyltransferase polymorphism (homozygous rapid acetylator,Bio. 87.20; homozygous slow acetylator, Bio. 82.73/H; and heterozygousacetylator, Bio. 87.20 x Bio. 82.73/H F₁), were investigatedfor the relationship of arylamine N-acetyltransferase to theAcCoA-dependent metabolic activation of carcinogenic N-hydroxy(N-OH)-arylamines to bind to DNA (O-acetyltransferase). Thelevels of both 2-aminofluorene (AF) N-acetyltransferase andN-OH-AF O-acetyltransferase activity reflected the N-acetylatorgenotype in liver, intestine, kidney and lung cytosols. A significantacetylator gene—dose response for AF N-acetyltransferaseand N-OH-AF O-acetyltransferase activities was observed in liverand lung cytosols. In contrast, acetylator genotype was notconsistently expressed for the AcCoA-dependent N-acetylationof 4-aminobiphenyl (ABP), nor for the AcCoA-dependent metabolicactivation of N-OH ABP and N-OH-3,2'-dimethyl-4-aminobiphenylin these me tissue cytosols. Two peaks of acetyltransferaseactivity were partially purified by ion exchange FPLC chromatographyfrom the hepatic cytosol of both the homozygous rapid and homozygousslow acetylator hamster. In contrast to unfractionated cytosol,the isozyme(s) eluting first clearly demonstrated levels ofAcCoA-dependent arylamine N-acetyltransferase and N-OH-arylamineO-acetyltransferase activities that were consistent with N-acetylatorgenotype (polymorphic) for all substrates tested. In contrast,the slower eluting isozyme(s) in each acetylator cytosol showedlevels of AcCoA-dependent N-and O-acetyltransferase activitiesthat did not vary with N-acetylator genotype (monomorphic).The AcCoA-dependent O-acetyltransferase activity of both themonomorphic and polymorphic peaks was paraoxon resistant. Thesestudies demonstrate acetylator genotype-dependent control ofAcCoA-dependent metabolic activation of N-OH-arylamines(O-acetylation)by polymorphic isozyme(s) similar to that for AcCoA-dependentN-acetylation of arylamines in the hamster. The polymorphicgenetic control of N-OH arylamine O-acetyltransferase may bean important risk factor for arylamine-induced cancer, in thosespecies and tissues expressing appreciable levels of O-acetyltransferaseactivity.     

Neural cell adhesion molecules are present in the fetal human primary olfactory pathway.

Olfactory tissues from human fetuses (17.5-28 weeks of gestation) were stained by immunofluorescence for neural cell adhesion molecules (N-CAMs). Staining for N-CAMs was most prominent in the olfactory nerve bundles in the lamina propria, while in the olfactory epithelium, it was present on the olfactory receptor neurons and globose basal cells. The basal cells proper and supporting cells lacked N-CAMs. In the olfactory bulb, only the olfactory nerve and glomerular layers showed moderate labeling for N-CAMs. Western blot analysis showed that the N-CAMs of the fetal human primary olfactory pathway consisted of three molecular isoforms, N-CAM180, N-CAM140 and N-CAM120.