Appropriateness of hysterectomy in Taiwan.

BACKGROUND AND PURPOSE: Hysterectomy is among the most frequently performed surgical procedures in developed countries, but few studies from the Asia-Pacific region have assessed the appropriateness of hysterectomy. The purpose of this study was to examine the rate of inappropriate hysterectomy in Taiwan and its association with patient characteristics and indications for the procedure. METHODS: A random sample of hysterectomies for which claims were submitted to the Taiwan Bureau of National Health Insurance from July 1, 1997 to June 30, 1998 was selected. A total of 658 charts were reviewed by an expert panel composed of 5 senior gynecologists. RESULTS: Overall, 74.2% of patients underwent hysterectomy for appropriate reasons, 5.6% for uncertain reasons, and 20.2% for inappropriate reasons. Inappropriate procedures were positively associated with younger age and premenopausal status. Primary indications that accounted for over 25% of inappropriate procedures were chronic pelvic pain (42.9%), abnormal uterine bleeding (37.5%), and endometriosis (27.7%). CONCLUSIONS: This study found a high rate of inappropriate hysterectomy in Taiwan. Gynecologists and physician organizations should take action to improve physician agreement on the use of hysterectomy, especially for indications associated with high rates of inappropriate procedures.     

Anterior lateral thigh flap for buccal mucosal defect after resection of buccal cancer.

OBJECTIVE: To preserve oral function after buccal cancer resection, a free anterior lateral thigh flap (ALTF) was used to cover the buccal mucosal defect. STUDY DESIGN AND SETTING: Nine patients who underwent primary surgical treatment between June 2005 and September 2006 for buccal cancer were enrolled in this study. An ALTF was used to repair the defect immediately after tumor resection. Oral function, including mouth-opening width, oral intake, and teeth cleaning, were compared pre- and postoperatively. RESULTS: No difference was observed in the mouth-opening width between that preoperatively and three months postoperatively (P = 0.54). The oral intake and teeth cleaning also remained unchanged three months postoperatively. CONCLUSION: Repair of a buccal mucosa defect with a free anterior lateral thigh flap is a good alternative for selected patients who undergo resection of buccal cancer; oral function is likely to be preserved.     

Transdermal Dual-Controlled Delivery of Contraceptive Drugs: Formulation Development,in Vitro and in Vivo Evaluations,and Clinical Performance

Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17-estradiol (E₂), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E₂ from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia–Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45°C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm²). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects.     

Irregular connexin43 expressed in a rare cardiac hamartoma containing adipose tissue in the crista terminalis

Cardiac hamartomas are very rare and are demarcated masses of enlarged, hypertrophied, mature myocytes and collagen tissue. Cardiac hamartomas are generally circumscribed in the right ventricle or atrium, but not reported in the crista terminalis (CRT). The CRT is crucial in electrophysiology, is related to arrhythmogenesis, and is targeted by radiofrequency catheter procedures. Previous works only described the benign natures of prominent CRT using non-invasive methods. This study describes an unusual cardiac hamartoma originating from the CRT and extending toward the tricuspid valve. Microscopically, this hamartoma comprised dense collagen and adipose tissue, mixed with hypertrophy, but with disarrayed cardiomyocytes. An irregular gap junction, connexin43, was demonstrated in this cardiac hamartoma.     

A new model for inflammation-induced preterm birth: the role of platelet-activating factor and Toll-like receptor-4

Preterm birth is a leading cause of neonatal morbidity and mortality. Despite a growing body of evidence correlating inflammation with preterm birth, the signal transduction pathways responsible for the emptying of the uterus in the setting of intrauterine inflammation has not been elucidated. We now report a unique, reproducible mouse model of localized intrauterine inflammation. This model results in 100% preterm delivery with no maternal mortality. Using our model, we also show that platelet-activating factor is a crucial mediator of both inflammation-induced preterm birth and fetal demise. Using C3H/HeJ mice, we demonstrate that toll-like receptor-4 (TLR-4) plays a role in lipopolysaccharide-induced preterm birth but not in inflammation-induced fetal death. Immunohistochemistry studies demonstrate the presence of the platelet-activating factor receptor in both endometrial glands and smooth muscle in uterine tissues. Molecular studies demonstrate the differential expression of platelet-activating factor receptor and TLR-4 in uterine and cervical tissue throughout gestation. Quantitative polymerase chain reaction revealed an up-regulation of TLR-4 in the fundal region of the uterus in response to intrauterine inflammation. The use of this model will increase our understanding of the significant clinical problem of inflammation-induced preterm birth and will elucidate signal transduction pathways involved in an inflammatory state.     

Neck proprioception compensates for age-related deterioration of vestibular self-motion perception

Vestibular functions are known to show some deterioration with age. Vestibular deterioration is often thought to be compensated for by an increase in neck proprioceptive gain. We studied this presumed compensatory mechanism by measuring psychophysical responses to vestibular (horizontal canal), neck and combined stimuli in 50 healthy human subjects as a function of age (range 15–76 years). After passive horizontal rotations of head and/or trunk (torso) in complete darkness (dominant frequencies 0.05, 0.1, and 0.4 Hz), subjects readjusted a visual target to its remembered prerotational location in space. (1) Vestibular-only stimulus (whole-body rotation); subjects' responses were shifted towards postrotatory body position, this only slightly at 0.4 Hz and pronounced at 0.1 and 0.05 Hz. These errors reflect the known physiological drop of vestibular gain at low rotational frequency. They exhibited a slight but significant increase with age. (2) Neck-only stimulus (trunk rotated, head stationary); the responses showed errors similar to those upon vestibular stimulation (with offset towards postrotatory trunk position) and this again slightly more with increasing age. (3) Vestibular-neck stimulus combination during head rotation on stationary trunk; the errors were close to zero, independent of stimulus frequency and the subjects' age. (4) Opposite stimulus combination (trunk rotated in the same direction as the head, but with double amplitude); the errors were clearly enhanced, essentially reflecting the sum of those with vestibular-only and neck-only stimulation. Taken together, we find a parallel increase in neck- and vestibular-related errors with age, in seeming contrast to previous studies. We explain our and the previous findings by a vestibular-neck interaction model in which two different neck signals are involved. One neck signal is used, in combination with the vestibular signal, for estimating trunk-in-space rotation. It is internally shaped to always match the vestibular signal, so that these two signals cancel each other out when summed during head rotation on stationary trunk. Because of this matching, perceived trunk stationariness during head rotation on the stationary trunk is independent of vestibular deterioration (related to stimulus frequency, age, ototoxic medication, etc.). The other neck proprioceptive signal, coding head-on-trunk rotation, is superimposed on the estimate of trunk-in-space rotation, thereby yielding a notion of head-in-space. This neck signal remains essentially unchanged with vestibular deterioration. Generally, we hold that the transformation of the vestibular signal from the head down to the trunk proceeds further to include the hip and the legs as well as the haptically perceived body support surface; by this, subjects yield a notion of support kinematics in space. As a consequence, spatial orientation is impaired by chronic vestibular deterioration only to the extent that the body support is moving in space, while it is unimpaired (determined by proprioception alone) during body motion with respect to a stationary support. Electronic Publication     

Cryptococcal glucuronoxylomannan inhibits adhesion of neutrophils to stimulated endothelium in vitro by affecting both neutrophils and endothelial cells

Cryptococcal infections are often characterized by a paucity of leukocytes in the infected tissues. Previous research has shown that the capsular polysaccharide glucuronoxylomannan (GXM) inhibits leukocyte migration. In this study we investigated whether the capsular polysaccharide GXM affects the migration of neutrophils (polymorphonuclear leukocytes [PMN]) through the endothelium by interfering with adhesion in a static adhesion model. Pretreatment of PMN with GXM inhibited PMN adhesion to tumor necrosis factor alpha (TNF-alpha)-stimulated endothelium up to 44%. Treatment of TNF-alpha-stimulated endothelium with GXM led to a 27% decrease in PMN adhesion. GXM treatment of both PMN and endothelium did not have an additive inhibitory effect. We demonstrated that GXM-induced L-selectin shedding does not play an important role in the detected inhibition of adhesion. L-selectin was still present on PMN in sufficient amounts after GXM treatment, since it could be further inhibited by blocking antibodies. Furthermore, blocking of GXM-related L-selectin shedding did not abolish the GXM-related inhibition of adhesion. GXM most likely exerts its effect on PMN by interfering with E-selectin-mediated binding. The use of blocking monoclonal antibodies against E-selectin, which was shown to decrease adhesion in the absence of GXM, did not cause additive inhibition of PMN adhesion after GXM pretreatment. The use of blocking antibodies also demonstrated that the inhibiting effect found after GXM treatment of endothelium probably involves interference with both intercellular adhesion molecule-1 and E-selectin binding.     

Detection of antibodies specific to an antigenic cell wall galactomannoprotein for serodiagnosis of Aspergillus fumigatus aspergillosis

Aspergilloma and invasive aspergillosis are important opportunistic infections caused by Aspergillus species, among which Aspergillus fumigatus is the most common species associated with human disease. We developed an enzyme-linked immunosorbent assay (ELISA)-based antibody assay with Afmp1p, a purified recombinant antigenic cell wall galactomannoprotein of A. fumigatus. Evaluation of the test with guinea pig sera against A. fumigatus and other pathogenic fungi indicated that this assay was specific for A. fumigatus. Clinical evaluation revealed that the assay was 100% sensitive for patients with aspergilloma and 33.3% sensitive for patients with invasive aspergillosis. No false-positive results were found for serum samples from 80 healthy blood donors, 6 patients with typhoid fever, 4 patients with melioidosis, 20 patients with penicilliosis marneffei, 5 patients with candidiasis, and 4 patients with cryptococcosis, indicating a high specificity of the test. Thus, this ELISA-based test for the detection of anti-Afmp1p antibody can be of significant value as a diagnostic for aspergillosis.