Characteristics of unrecognised bipolar disorder in patients treated for major depressive disorder in China: general versus psychiatric hospitals.

OBJECTIVES: Bipolar disorder is often misdiagnosed as major depressive disorder. Such misdiagnosis partly depends on the type of treatment setting. This study compared general hospital psychiatric units with psychiatric hospitals in China with respect to basic demographic and clinical characteristics of patients with unrecognised bipolar disorder who are treated for major depressive disorder. METHODS: Patients treated for major depressive disorder were consecutively examined in 13 health centres (6 general hospital psychiatric units and 7 psychiatric hospitals) in China. Their socio-demographic and clinical features were recorded using a standardised protocol and data collection procedure. The DSM-IV diagnoses were established using the Mini-International Neuropsychiatric Interview. RESULTS: Of the 1487 patients included in the study, 309 (20.8%) were diagnosed with bipolar disorder. There was no significant difference between general hospital psychiatric units and psychiatric hospitals in the ratio of all types of unrecognised bipolar disorders (χ2 = 0.008, degrees of freedom = 1, p = 0.9) and bipolar II disorders (χ2 = 3.1, degrees of freedom = 1, p = 0.08). The proportions of unrecognised bipolar I disorders (χ2 = 4.1, degrees of freedom = 1, p = 0.04) differed significantly between the 2 types of study site. Multivariate analyses showed that patients with bipolar I disorders with more seasonal depressive episodes were more likely to receive treatment in general hospital psychiatric units (odds ratio = 3.3, 95% confidence interval = 1.1-9.8). CONCLUSION: Patients with bipolar I disorders receiving treatment in general hospital psychiatric units had different clinical characteristics compared to their counterparts treated in psychiatric hospitals in China.

Further evidence for the association between G72/G30 genes and schizophrenia in two ethnically distinct populations.

Recently, the nested genes G72 and G30 on chromosome 13q32-q33 have been implicated in the etiology of schizophrenia. We genotyped six single-nucleotide polymorphisms (SNPs: rs3916965, rs3916967, rs2391191, rs778294, rs779293 and rs3918342), which span approximately 82.5 kb in the region encompassing the G72/G30 genes in 1176 Han Chinese subjects (588 cases and 588 controls) and 365 Scottish subjects (183 cases and 182 controls). Significant association between an allele of marker rs778293 and schizophrenia was found in our Chinese samples (P = 0.0013), and was replicated in the Scottish samples (P = 0.022). LD analysis revealed that four SNPs between rs3916965 and rs778294 were in LD, called block I, and the two distal SNPs (rs778293 and rs3918342) constituted a block II in both the Chinese and Scottish samples. We selected one SNP from each block (rs778294 from block I and rs778293 from block II), and then analyzed the haplotypes. A significant difference was observed for the common haplotype GC in the Chinese sample (P = 0.0145), and was replicated in the Scottish sample (P = 0.003). On meta-analysis, we separately analyzed the studies in Asian and European populations because of significant heterogeneity in the homogeneity test. We found a statistically significant association between rs778293 and schizophrenia in Asian populations, but no difference was found between cases and controls in the European populations. Overall, our data give further support to the existing evidence that G72/G30 genes are involved in conferring susceptibility to schizophrenia.

Effect of the protein kinase C inhibitor, staurosporine, on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801).

RATIONALE: In our preliminary study, methamphetamine (METH) at 2.5 mg/kg, but not at 1.0 mg/kg, induced a delayed increase in glutamate levels in the nucleus accumbens (NAc). We hypothesize that repeated increases in glutamate levels produces behavioral sensitization to a selective uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK-801), and that an activation of protein kinase C (PKC) plays an important role for this sensitization. OBJECTIVES: This study was conducted to confirm delayed increases in glutamate levels induced by a higher dose of METH (2.5 mg/kg), and to examine the effect of straurosporine, a PKC inhibitor, on the higher dose of METH-induced sensitization to dizocilpine. METHODS: The effects of METH on extracellular glutamate levels in the NAc were studied using in vivo microdialysis. Locomotor activity was measured by using an infrared sensor. RESULTS: METH at 2.5 mg/kg, but not at 1.0 mg/kg, induced delayed increases in glutamate levels. The acute administration of staurosporine did not affect the locomotor activity by a single injection of METH (2.5 mg/kg). Repeated METH administrations (2.5 mg/kg, once in every other day, for five times) developed behavioral sensitization to the locomotion-inducing effect of dizocilpine (0.2 mg/kg), a selective uncompetitive NMDA receptor antagonist. Staurosporine (0.1 mg/kg), given 120 min later for every METH treatment, inhibited the development of behavioral sensitization to dizocilpine. CONCLUSIONS: These results suggest the involvement of increased glutamate levels and an activation of PKC in delayed-induced synaptic and cellular plasticity underlying the higher dose of METH-induced behavioral sensitization to dizocilpine.

Facial subdermal vascular network flap: anatomic study and clinical application.

Despite the numerous flaps for facial reconstruction that have been described, the search for the ideal flap with good color matching and minimal donor-site morbidity continues. In the past 3 years we have repaired 13 facial defects with success using the lateral genicervical flap - a type of facial subdermal vascular network flap (SVNF) - with a pedicle located on the preauricular region. An anatomic study of the facial SVNF, including blood supply and vascular distribution of the face and anatomic characteristics of facial vessels, based on 14 cadaver dissections, was carried out. The blood supply of the facial skin basically originated from the branches of the facial, superficial temporal and infraorbital arteries. The lateral genicervical skin was supplied basically by the branches of the facial, superficial temporal and occipital arteries, but also by the terminal branches of the superior thyroid artery. The branches diverging from these arteries became superficial and formed a subcutaneous arterial network. The arterioles from the network went to the corium layer and formed a subdermal arterial network whose arterioles anastomosed with each other in a honeycomb-like structure. The vascular distribution presented certain directivity on different areas. The blood supply of the pedicle originated from the subdermal vascular network formed by the perforator branches of these arteries. The arterioles from the facial and superficial temporal arteries anastomosed in the lateral genicervical region. From the anatomic study, we think that the viability of the facial SVNF depends basically on the subdermal vascular network formed by the perforator branches of the pedicle, and that the anastomoses between the facial and superficial temporal arteries provide a solid anatomic basis to the lateral genicervical flap. The clinical data also indicated that this flap is a useful alternative for facial, especially superficial temporal, defects. But the directivity must be taken into account in its clinical application.

An unusual cutaneous metastasis from hepatocellular carcinoma.

Cutaneous metastases from hepatocellular carcinoma are rare. In this report we detail a case of hepatocellular carcinoma with the unusual manifestations of multiple skin metastases. A 49-year-old male, who had received surgical resection of hepatocellular carcinoma one year prior, presented with multiple reddish-blue, firm, painless and nonulcerative cutaneous papules and nodules over the fingers, palms, toes, soles and back. Pathology of the cutaneous nodules showed characteristic hepatocellular carcinoma with trabecular gland formation. These lesions grew very rapidly and developed to cauliflower appearances which had not been described previously in the literature. The patient died of respiratory failure secondary to lung metastasis two months after the first appearance of the skin lesions.

Transcriptional mRNA of bone morphogenetic proteins 2, 3, 4, and 5 in trigeminal nerve, benign and malignant peripheral nerve sheath tumors.

Bone morphogenetic proteins (BMPs) have been shown to play an important role in cell growth and differentiation. BMPs, a rapidly expanding family closely related to transforming growth factor-beta (TGF-beta) superfamily, have been proven recently to possess a regulatory role and neurotrophic capacity in neurogenesis. The aim of the present study is to reveal the relationship among BMPs, peripheral nerve and neoplastic lesions of nerve sheath tumors. The mRNA transcriptions of BMP 2, 3, 4 and 5 in 12 cases of schwannoma, four cases of malignant schwannoma and three cases of trigeminal neuralgia were detected using an in situ hybridization technique. Our results demonstrated that the myelin sheaths of schwann cell from the peripheral neuroectomy of trigeminal neuralgia were positively expressing mRNA of BMP-2, 3, 4 and 5. However, the nerve fibers of trigeminal nerve showed only BMP-2 positive staining. All of the neoplastic lesions of nerve sheath showed a consistent but variant expression of BMP-2, 3, 4, and 5. Except for the BMP-4 mRNA, the expression signals of BMP-2, 3 and 5 mRNA in malignant schwannoma were relatively lower than in benign lesions. On the basis of the findings, we concluded that selected members of BMPs existed in the peripheral nerves and might contribute to the health maintenance, proliferation, regeneration and neoplastic transformation of the peripheral nerve system. Moreover, the effects of BMP-2, 3, 4 and 5 on peripheral nerve system and its neoplastic transformation might be widespread, diverse and antagonistic.

Detection of HPV in Japanese and Chinese oral carcinomas by in situ PCR.

Human papillomavirus (HPV) is established as the cause of almost 100% of cervical carcinomas. However, the association of HPV with oral squamous cell carcinomas (SCCs) is less well understood. We examined the prevalence of HPV in oral SCCs in samples of Japanese and Chinese populations. Using in situ polymerase chain reaction (PCR) analysis (MY09 and MY11 consensus primers), HPV was detected in the nucleus of epithelia and tumor cells in oral lesions. Analysis revealed the specific presence of HPV DNA in all cases of SCC in our Japanese (10/10) and Chinese (10/10) population samples. These results suggest that HPV infection could be one of several risk factors contributing to oral SCC in Japanese and Chinese.

Alteration of apoptosis in cleft palate formation and ectomesenchymal stem cells influenced by retinoic acid.

It has been shown that apoptosis is involved in normal embryonic development. The aim of the present study was to elucidate the role and alteration of apoptosis in the pathogenesis of cleft palate induced by retinoic acid (RA) and the ectomesenchymal stem (EMS) cells influenced by RA. RA was administered by gavage to pregnant C57BL/6N strain mice in the experimental group, and the control group received oil alone. Pregnant mice were killed at set periods of time thereafter and histologically analyzed. EMS cells explanted from the palatal shelves of embryonic mice were cultured and characterized by immunohistochemistry, growth curves and population-doubling time. The alterations of apoptosis of EMS cells and developing palatal shelves influenced by RA were evaluated by the terminal deoxynucleotidyl transferase-mediated UTP-biotin nick end-labeling (TUNEL) method. RA-treated mice showed formation of cleft palates resulted from the small size of the palatal shelves and their failure to lift. TUNEL staining showed that the number of apoptotic mesenchymal cells in palatal shelves in the RA-treated mice was increased significantly when compared with the control group. The primary culture of EMS cells proceeded successfully. The population-doubling time of RA-treated cells was much longer compared with non-treated EMS cells. RA also dramatically increased the number of apoptotic cells in EMS cells in vitro. We concluded that EMS cells are the crucial cells in palate development. RA could inhibit the proliferation and induced the apoptosis of EMS cells. The inhibition of growth and excess apoptosis of EMS cells may contribute to the formation of cleft palate and other orofacial congenital malformations.

Total intravenous anesthesia using propofol and ketamine for ambulatory gynecologic laparoscopy.

Laparoscopy under total intravenous anesthesia (TIVA) with spontaneous respiration is a commonly encountered procedure in ambulatory gynecologic surgery. The purpose of this study was to evaluate the efficacy of TIVA using propofol and ketamine, compared with endotracheal inhalational general anesthesia (EIGA) for ambulatory gynecologic laparoscopy. Fifty-eight female patients, aged 17-48 years, were randomly allocated into two groups. Group 1 (TIVA) (n = 28) received propofol at the induction of anesthesia followed by propofol infusion for maintenance. Intravenous ketamine 0.5 mg/kg was administered before operation for anesthetic effect. Natural airway and spontaneous breathing were then maintained in patients. Group 2 (n = 30) received EIGA with isoflurane under controlled ventilation. We found that the two groups demonstrated similar trend characters of pH and PaCO2 during operation and in recovery room. The incidence of postoperative vomiting was higher in group 2 than in group 1 (30% vs. 7%; p < 0.05). The incidence of intraoperative arrhythmia was higher in group 2 than in group 1 (40% vs. 3%; p < 0.001). Furthermore, the incidence of sore throat was higher in group 2 than in group 1 (47% vs. 7%; p < 0.001). We conclude that TIVA with spontaneous respiration is suitable for ambulatory gynecologic laparoscopy.

SEM study on microvascular changes following implantation of bone morphogenetic protein combined with hydroxyapatite into experimental bone defects.

BMP-HAP complex was implanted into a bone defect in the femur of Wistar-strain rats, and animals were allowed to heal for one to 8 weeks prior to sacrifice. Similar bone defects without BMP-HAP complex served as controls. Osseous healing and microvascular changes, as revealed by plastic microcorrosion castings, were subsequently examined under a scanning electron microscope. One week after implantation, sproutings and congregate sinusoidal capillary plexuses and primary bone trabeculae (woven bone) were observed around and between the BMP-HAP complexes. Control specimens revealed a fine and immature sinusoidal capillary plexus arising from sproutings and elongations of pre-existing blood vessels, but bone formation was not observed. At two weeks, newly-formed trabeculae were observed around and on the surface of the HAPs, and a network of thick, newly-formed vessels was observed in intervening space. At three weeks, networks of newly-formed vessels were observed on the surface of the HAPs, and surrounding newly-formed trabeculae had become thickened. At four weeks, bone defects were filled, and HAP was completely embedded in new bone. At eight weeks, the HAP was fused with new bone, and the boundary between the HAP and new bone was unclear. In comparison with comparable surgically created control bone defects without implanted BMP-HAP complex, BMP apparently stimulates new vascularization. Further, implanted BMP-HAP apparently stimulates undifferentiated mesenchymal cells to differentiate into angioblasts and osteoblasts, or vice versa (dedifferentiation).

A new method of determining chlorine kinetic isotope effects.

Two methods have been used to measure the chlorine leaving group kinetic isotope effect for the S(N)2 reduction of benzyl chloride to toluene by sodium borohydride in DMSO at 30.000 °C. The reaction was monitored by titrating the unreacted borohydride ion. One method involved determining the chlorine isotope effect using the classical IRMS method, which requires the conversion of the chloride ions into gaseous methyl chloride that is analyzed in an isotope ratio mass spectrometric analyses (Hill, J. W.; Fry, A. J. Am. Chem. Soc. 1962, 84, 2763. Taylor, J. W.; Grimsrud, E. P. Anal. Chem. 1969, 41, 805.). Two different measurements using this method yielded isotope effects of k(35)/k(37) = 1.007 19 ± 0.000 19 and 1.007 64 ± 0.000 19. The second method was a new technique where the ratio of the chlorine isotopes was obtained by fast atom bombardment mass spectrometry on the silver chloride recovered from the reaction, i.e., from the first step in the classical procedure. Therefore, the new method is much simpler and avoids the time-consuming preparation, purification, and recovery of the gaseous methyl chloride. Although the experimental error is larger (k(35)/k(37) = 1.008 03 ± 0.00 10 and 1.008 02 ± 0.000 65) when the new technique is used to analyze the silver chloride samples from the same set of experiments that were used to measure the isotope effect by the classical method, the chlorine isotope effect found by the two methods is identical within experimental error. This large chlorine kinetic isotope effect indicates there is considerable C(α)-Cl bond rupture in the S(N)2 transition state.

Experimental ligation versus embolization of the external carotid artery: a comparative hemodynamics study.

Patterns of collateral vascularization were investigated by SEM evaluation of microvascular corrosion casts following either ligation or embolization of the external carotid artery in the rabbit. Results indicated that rich collateral channels were established soon after ligation of this artery, and blood supply to the lesional area was never cut off. In contrast, embolization effectively obstructed blood supply by reducing collateral branches. We concluded that for purposes of controlling blood loss, it is more helpful to employ external carotid embolization rather than ligation for oral maxillofacial lesions with a rich blood supply.

Photoacoustic ultrasound (PAUS)--reconstruction tomography.

The theoretical underpinnings of photoacoustic ultrasound (PAUS) reconstruction tomography are presented. A formal relationship between PAUS signals and the heterogeneous distribution of optical absorption within the object being investigated is developed. Based on this theory, a reconstruction approach, analogous to that used in x-ray computed tomography, is suggested. Initial experimental results suggest that this approach produces "reasonable" reconstructions for absorbers distributed within a narrow plane embedded within a highly scattering medium.

Alcohol and aldehyde dehydrogenase genotypes and drinking behavior of Chinese living in Shanghai.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the principal enzymes responsible for oxidative metabolism of ethanol, exist in multiple, genetically determined molecular forms. Widely different kinetic properties in some of these isozymes account for the individual differences in alcohol sensitivity. In this study we used the polymerase chain reaction/restriction fragment length polymorphism method to determine the genotypes of the ADH2 and ALDH2 loci of alcoholic and nonalcoholic Chinese living in Shanghai. We also investigated the subjects' drinking patterns by means of semistructured interviews. The alcoholics had significantly lower frequencies of the ADH2(2) and ALDH2(2) alleles than did the nonalcoholics, suggesting the inhibitory effects of these alleles for the development of alcoholism. In the nonalcoholic subjects, ADH2(2) had little, if any, effect, despite the significant effect of the ALDH2(2) allele in decreasing the alcohol consumption of the individual. Taken together, these results fit the proposed hypothesis for the development of alcoholism, i.e., drinking behavior is greatly influenced by the individual's genotypes of alcohol-metabolizing enzymes, and the risk of becoming alcoholic is proportionate with the ethanol consumption of the individual.

The inductive effect of bone morphogenetic protein (BMP) on human periodontal fibroblast-like cells in vitro.

Bone morphogenetic protein (BMP) has the capability of 1) inducing bone formation in non-bone tissue such as muscle, 2) promoting proliferation and differentiation of human dental pulpal cells, and 3) inducing early formation of both osteodentin and regular tubular dentin. In addition, when BMP is implanted in periodontal defects, it stimulates regeneration of periodontal tissues. In the present study, we sought to explore the mechanisms by which BMP induces these effects, using immunohistochemical methods to investigate periodontal fibroblast-like cells in vitro. Cellular production of fibronectin, endogenous BMP and alkaline phosphatase were measured using image analysis of immunohistochemical reactivity. Periodontal fibroblast-like cells incubated with exogenous BMP showed decreased alkaline phosphatase activity, unchanged fibronectin production, but increased expression of endogenous BMP compared with control specimens incubated without BMP. These data suggest that regenerative as well as inductive effects of BMP on undifferentiated periodontal mesenchymal cells may be mediated through its ability to modulate cellular expression of these substances.

Induction of reparative dentin formation in dogs by bovine bone morphogenetic protein bound to ceramic dentin.

Bone morphogenetic protein (BMP) refers to a group of bone-inducing growth factors used to enhance experimental osseous repair. Previous studies have indicated that BMP promotes the proliferation and differentiation of fibroblasts from human dental pulp both in vitro and in vivo. Furthermore, when BMP is used as a pulp capping agent, it has ability to induce the formation of both osteodentin and tubular dentin. In this study, we sought to explore whether or not BMP, complexed to ceramic dentin (BMP/CD), would constitute a more effective pulp capping agent than BMP alone. Experimental pulp exposures were created in dogs, and BMP/CD was placed on the surface of the exposed dental pulp. The inductive effect of such stimulation on reparative dentin formation was observed morphologically. Results showed that two weeks after exposure, some osteodentinal matrix was formed in the space surrounding the implanted BMP/CD particles while the remainder of the space was occupied by proliferating fibroblasts. At 4 weeks postoperatively, the dential bridge was complete. When ceramic dentin without BMP was used, there was minimal bone-like matrix formed even at 4 weeks postoperatively. These results suggest that the BMP/CD complex is effective as a stimulant of reparative dentin formation and shows potential as a therapeutically useful pulp-capping agent in a clinical setting.

Ability of hydroxyapatite-bone morphogenetic (corrected from morphologenetic) protein (BMP) complex to induce dentin formation in dogs.

This histological investigation examined the formation and differentiation of pulp cells under the influence of HAP/BMP complex. HAP/BMP complex was implanted in exposed pulp of the mandibular premolars and alveolar bone defect in the dog. Sequential changes in these areas were examined mainly under a light microscope and partly under a scanning electron microscope. Two weeks after the operation, fibroblast-like cells proliferated right beneath the implanted complex, and after 3 weeks, dentin including dentin tubules grew in the pulp. After four weeks a dentin bridge composed of osteoid dentin was found, and after 8 weeks this dentin calcified and covered the defective surface of the root and adhered to new bone surrounding the HAP granules. The results indicated that the dentin induced by HAP/BMP complex may be of two types: tubular dentin and osteodentin. This complex exhibited outstanding ability to induce dentinogenesis and osteogenesis.

[A case of the right subclavian artery as the last branch of the aortic arch in the human fetus and a new classification on these variations].

An anomalous case of the right subclavian artery arising from the aortic arch as the last branch, in which the first branch was the right common carotid, the second the left common carotid and the third the left subclavian artery, was found in a 10 months human fetus among 173 fetuses. The right subclavian artery arose from the posterior wall of the aortic arch at the level of the Th4 and passed obliquely between the esophagus and the thoracic vertebrae. The right and the left vertebral arteries arising from the subclavian arteries on the same side entered the transverse foramen of the C6 of each side. This case belonged to type G of Adachi's classification and as well type 5 of Holzapfel's. The present authors wish to offer a new trial classification on these variations, including the origins and numbers of the vertebral arteries, by investigating many original reports in Japanese, as follows: 1) A new classification is fixed on the basis of the type G and H of Adachi-Williams et al.-Nakagawa in the classification of the branching types of the aortic arch. The type G represents that the right common carotid, the left common carotid, the left subclavian and the right subclavian arteries arise from the aortic arch in this order. The type H represents that the bicarotid trunk, the left subclavian and the right subclavian arteries arise from the aortic arch. 2) When the left vertebral artery arising from the aortic arch is found in the type G and H, "C" is prefixed G or H, as type CG, type CH. 3) When the right vertebral artery arising from the right common carotid artery is found, a prime mark, ""', is put on G or H, as type G', type H'. 4) In order to represent a compound type of the above 2) and 3), both "C" and ""' are put, as type CG', type CH'. 5) When the bilateral vertebral arteries arising from the respective subclavian artery are found in the above 2), 3) and 4) "2" postfixed "C" and the prime mark ""', as type G'2, type C2G, type CG'2, type C2G', type C2G'2, type H'2, type C2H, type CH'2, type C2H', type C2H'2. According to the above new classification, Adachi's type G can be arranged into 18 branching types. This classification may be helpful and sufficient to provide more than 100 cases of the type G and H reported on Japanese.(ABSTRACT TRUNCATED AT 250 WORDS)