Prospective comparison of the therapeutic effect of teriparatide with that of combined vertebroplasty with antiresorptive agents for the treatment of new-onset adjacent vertebral compression fracture after percutaneous vertebroplasty.

UNLABELLED: Most post-vertebroplasty new-onset adjacent vertebral compression fractures (VCFs) occur within 2-3 months, and antiresorptive agents do not significantly reduce the risk of their occurrence. In opposite mechanism, teriparatide directly stimulates bone formation and improves bone strength and quality faster. The therapeutic effect of teriparatide is better than that of vertebroplasty combined with an antiresorptive treatment and is a potentially useful therapy for new-onset adjacent VCFs after vertebroplasty. INTRODUCTION: Following vertebroplasty, patients are at increased risk of new-onset adjacent-level VCFs. The therapeutic effect of antiresorptive agents is too slow, and they are associated with the risk of new VCFs. Teriparatide markedly increases bone formation and strength and reduces the incidence of new-onset VCFs. This prospective cohort study compared the therapeutic effects of teriparatide with those of combined vertebroplasty and an anti-resorber for treating new-onset adjacent VCFs after vertebroplasty. METHODS: Fifty patients with adjacent VCFs were randomly assigned to two groups: teriparatide only (group A) and additional vertebroplasty combined with an antiresorptive agent (group B). Relevant clinical data of the two groups were prospectively compared. RESULTS: The 22 patients in group A were at higher risk of new VCFs than those in group B (22 patients); they were older and had more pre-existing fractures (p < 0.05). Patients treated with teriparatide had a significantly lower incidence of new-onset VCFs (odds ratio = 0.21; 95% confidence interval, 0.02-2.10). Teriparatide-mediated VCF reduction was 78.57%, which was markedly better than that of group B. The teriparatide group had a significant decrease in the visual analog scale and an increase in the Japanese Orthopedic Association low back pain score after 6 months of treatment (p < 0.05). The increase in lumbar spine BMD was marked in the teriparatide group (21.70% vs. 6.87%) after an 18-month treatment. CONCLUSIONS: Treatment of post-vertebroplasty adjacent VCFs with teriparatide (no new vertebroplasty) was more effective than that of repeated vertebroplasties combined with an anti-resorber.

Regular Tai Chi Chuan exercise improves T cell helper function of patients with type 2 diabetes mellitus with an increase in T-bet transcription factor and IL-12 production.

BACKGROUND: Exercise has been shown to be beneficial in the treatment of type 2 diabetes mellitus (DM); its benefit to immune function, however, remains to be determined. OBJECTIVE: This study investigated the effect of a 12-week course of Tai Chi Chuan (TCC) exercise on T cell helper (Th) reaction in patients with type 2 DM. METHODS: A case-control study was performed in 30 pairs of patients with type 2 DM and normal age-matched adults. Fasting blood glucose, HbA1c, mediators (interleukin (IL)-12, IL-4 and transforming growth factor (TGF)beta) and transcription factors (T-bet, GATA-3 and FoxP3) of Th1/Th2/T regulatory (Treg) reaction were measured before and after a 12-week TCC exercise programme. RESULTS: Fasting glucose and HbA1c levels in the patients with type 2 DM were significantly higher than in age-matched controls before exercise. After TCC exercise, HbA1c levels in patients with type 2 DM significantly decreased (7.59 (0.32)% vs 7.16 (0.22)%; p = 0.047) and blood levels of IL-12 increased significantly (5.96 (1.10) vs 12.96 (3.07); p = 0.035). To study the molecular Th1/Th2/Treg reaction, patients with type 2 DM were found to have lower T-bet but not GATA-3 or FoxP3 expression than normal controls before TCC exercise. After the 12-week TCC exercise T-bet expression significantly increased in patients with type 2 DM. CONCLUSIONS: A 12-week TCC exercise programme decreases HbA1c levels along with an increase in the Th1 reaction. A combination of TCC with medication may provide an even better improvement in both metabolism and immunity of patients with type 2 DM.

A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala.

Western blot analysis of neuronal tissues taken from fear-conditioned rats showed a selective activation of phosphatidylinositol 3-kinase (PI-3 kinase) in the amygdala. PI-3 kinase was also activated in response to long-term potentiation (LTP)-inducing tetanic stimulation. PI-3 kinase inhibitors blocked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, these inhibitors interfered with long-term fear memory while leaving short-term memory intact. Tetanus and forskolin-induced activation of mitogen-activated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which also inhibited cAMP response element binding protein (CREB) phosphorylation. These results provide novel evidence of a requirement of PI-3 kinase activation in the amygdala for synaptic plasticity and memory consolidation, and this activation may occur at a point upstream of MAPK activation.

Localization of a susceptibility locus for hepatocellular carcinoma to chromosome 4q in a hepatitis B hyperendemic area.

Chromosome 4q is one of the most common regions with a high frequency of allelic loss in hepatocellular carcinoma (HCC). To identify the HCC-susceptibility locus on chromosome 4q, we have performed linkage and family-based association analyses on Chinese families with HCC from Taiwan, where hepatitis B is hyperendemic. Using 77 microsatellite markers spanning chromosome 4q on 52 multiplex families, we found suggestive evidence of linkage to 4q22.3-28.1 with a maximum two-point heterogeneity LOD (HLOD) score of 2.55 at marker D4S3240 on chromosome 4q25. Multipoint analyses with microsatellite markers in the region 4q22.3-28.1 resulted in a maximum HLOD score of 3.12 and a maximum nonparametric linkage (NPL) Z score of 1.98 (pointwise P=0.0080; region-wide empirical P=0.021) for D4S3240. The evidence for linkage to D4S3240 was seen mostly in a subset of 28 families lacking affected parents, which showed multipoint HLOD and NPL scores of 3.25 and 2.79 (pointwise P=0.0028; region-wide empirical P=0.008), respectively. Family-based association analyses of the 77 microsatellite markers in 191 families (53 multiplex plus 138 singleton families) using the pedigree disequilibrium test provide further support for observed linkage. Additional genotyping in the 52 multiplex families informative for linkage analyses was performed for 29 single-nucleotide polymorphisms around D4S3240. A common haplotype (at markers rs7442180 and rs221330) positioned approximately 873 kb away from D4S3240 was associated with HCC, with P=0.0074.

Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells.

BACKGROUND: The duration and vigour of physical exercise are widely considered to be critical elements that may positively or negatively affect physical health and immune response. OBJECTIVES: To investigate the effect of a 12 week programme of regular tai chi chuan exercise (TCC) on functional mobility, beliefs about benefits of exercise on physical and psychological health, and immune regulation in middle aged volunteers. METHODS: This quasi-experimental research design involving one group with testing before and after the programme was conducted to measure the effect of 12 weeks of TCC exercise in 14 men and 23 women from the normal community. RESULTS: Regular TCC exercise had a highly significant positive effect on functional mobility (p = 0.001) and beliefs about the health benefits of exercise (p = 0.013) in the 37 participants. Total white blood cell and red blood cell count did not change significantly, but a highly significant (p<0.001) decrease in monocyte count occurred. A significant (p = 0.05) increase in the ratio of T helper to suppressor cells (CD4:CD8) was found, along with a significant (p = 0.015) increase in CD4CD25 regulatory T cells. Production of the regulatory T cell mediators transforming growth factor beta and interleukin 10 under specific antigen stimulation (varicella zoster virus) was also significantly increased after this exercise programme. CONCLUSIONS: A 12 week programme of regular TCC exercise enhances functional mobility, personal health expectations, and regulatory T cell function.

Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas.

Cytogenetic analysis of hepatocellular carcinoma (HCC) cell lines and primary HCC tissues has demonstrated chromosome 1p to be the region most commonly affected. To refine the altered locus, genetic abnormalities of this region were surveyed systemically by microsatellite polymorphism analysis. Twelve sets of primers evenly distributed on chromosome 1p which can amplify di- or tetranucleotide repeat length polymorphism by polymerase chain reaction were selected. The results were then supplemented by the conventional restriction fragment length polymorphism study. A comparison of the allele patterns between 30 pairs of HCC and their corresponding nontumor DNAs discovered chromosome 1p aberrations in 15 of 30 tumors (50%). The abnormalities can be classified into three groups. The first aberration was typical loss of heterozygosity that was found in 9 HCCs (30%). The second aberration was a 2-3-fold increase of allelic dosage, which was detected in 6 HCCs (20%). The third aberration was the novel microsatellite polymorphism, which was detected in 3 cases (10%). These abnormalities seemed to cluster at the distal part of chromosome 1p, with a common region mapped to 1p35-36, which is also the region with frequent loss of heterozygosity in neuroblastoma and colorectal and breast cancers. Therefore, loss of putative tumor suppressor gene(s) in this locus may participate in the development of hepatocellular carcinoma and a wide range of human cancers.

Age-dependent increase of mitochondrial DNA deletions together with lipid peroxides and superoxide dismutase in human liver mitochondria.

We previously reported an age-dependent deterioration of mitochondrial respiration as well as two age-associated mitochondrial DNA (mtDNA) deletions in the human liver. In this study, we further determined the relative quantities of the deleted mtDNAs in liver biopsies from 64 subjects of different ages. The results showed that both mtDNA deletions increase in frequency and quantity with age. Moreover, we measured hepatic lipid peroxides (malondialdehyde; MDA) of isolated mitochondria and manganese superoxide dismutase (Mn-SOD) activity of submitochondrial particles. We found a significant age-dependent increase in both MDA and Mn-SOD levels in liver mitochondria. These results confirm the previous contention that enhanced generation of lipid peroxides in the mitochondria during the aging process may damage mtDNA, and mtDNA deletions may be one of the important factors contributing to aging in humans.

Sequential scintiphotography with technetium-99m pyridoxylideneglutamate in the detection of intrahepatic lithiasis: concise communication.

Sequential scintiphotography with Tc-99m pyridoxylideneglutamate was used to evaluate patients under strong suspicion of intrahepatic stones. The scintiphotos of 19 cases were analyzed. Results indicate that the sequential study reveals an excretion pattern pertinent to the diagnosis of intrahepatic stone. This simple and innocuous approach would be a useful screening technique for this disease.

Technetium-99m-pyrophosphate scintigraphic findings of intestinal perforation in dermatomyositis.

Gastrointestinal complications are more common in children than in adults and present a serious problem with dermatomyositis. We report on a 66-yr-old man with dermatomyositis who suffered from intestinal perforation. The abdominal plain radiograph revealed only dilatation of the intestinal loops; increased radioactivity, however, was clearly demonstrated in the early 5-min and delayed 3-hr 99mTc-pyrophosphate images.

Comparative radionuclide imaging of metastatic insular carcinoma of the thyroid: value of technetium-99m-(V)DMSA.

We report a case of metastatic insular carcinoma of the thyroid evaluated with 201TI, 99mTc-MIBI, 99mTc-(V)DMSA, 99mTc-MDP and 131I whole-body scans, which were obtained after total thyroidectomy. For the majority of lesions detected in the skeleton and soft tissue, 131I images were generally available, although most were visualized easier with 99mTc-(V)DMSA. Technetium-99m-MDP images were considered better than 99mTc-(V)DMSA images in showing bone lesions but not soft-tissue lesions. Both 201TI and 99mTc-MIBI scans provided sufficient advantage to exhibit neck and mediastinal metastases, but they did not surpass 99mTc-(V)DMSA in detecting abdominal or bony lesions. In this patient with various metastases from insular carcinoma of the thyroid, 99mTc-(V)DMSA seemed to be the tracer of choice for whole-body imaging.

Xenon-133 hepatic retention ratio: a useful index for fatty liver quantification.

Xenon-133 hepatic retention ratio was developed for quantifying fatty liver. Data were acquired in frame mode in the hepatic region and both lung bases for 5 min after rebreathing 20 mCi of gaseous 133Xe and for another 5 min during washout. Static [99mTc]sulfur colloid liver imaging was performed with the patient in the identical position immediately after the ventilation study and data were stored for liver localization. A hepatic time-activity curve corrected for background activity was generated. The 133Xe retention ratio was derived by dividing the activity at 3.5 min after washout by the peak activity. The data of 16 controls and 20 patients with fatty liver were analyzed. The retention ratio (mean +/- s.d.) was greatly increased in patients with fatty infiltration (0.43 +/- 0.20 vs. 0.04 +/- 0.08 in controls, p less than 0.001). There was a strong positive correlation between the 133Xe retention ratios and percentage of fat on biopsy as assessed by the amount of the liver tissue occupied by fat globules on H & E stained sections. The 133Xe hepatic retention ratio is a simple, accurate and clinically useful index of detecting, quantifying and managing fatty infiltration of the liver.

Technetium-99m HIDA hepatic lobar distribution and retention ratios in detection of intrahepatic lithiasis.

Technetium-99m HIDA hepatic lobar distribution and retention ratios were developed to evaluate patients with intrahepatic lithiasis. The data of 57 cases were analyzed. Results reveal a highly significant difference in these ratios between the patients and normal individuals. They are simple, objective, and easily obtainable. Thus, the determination of these ratios may replace [99mTc]HIDA sequential scintiphotography, which is qualitative and time consuming, for screening intrahepatic lithiasis.

Transfer function analysis of the ventricular function: a new method for calculating right ventricular ejection fraction.

The relationship between the ventricular transfer function and ejection fraction has been investigated by the routine procedure of first-pass radionuclide angiocardiography. Ejection fraction has been shown to equal 1-e(-b), where b is the ratio of the R-R interval over the mean transit time difference between ventricular and atrial time-activity curves. To evaluate the effect of region of interest (ROI) on the right ventricular ejection fraction (RVEF), the results of the transfer function analysis (TFA) technique using precise ROI, TFA using rectangular ROI, and the routine method were compared. Regression analyses among RVEFs obtained from the above ROI methods yielded good correlations. Reliable RVEFs have been obtained even in the case of an improper bolus injection. Thus, the TFA technique is a new, simple, and reliable method for calculating RVEF without needing to outline the right ventricle precisely.

Technetium-99m-DMSA renal SPECT in diagnosing and monitoring pediatric acute pyelonephritis.

UNLABELLED: This study compares the sensitivity of 99mTc-dimercaptosuccinic acid (DMSA) renal SPECT with planar scintigraphy, concluding the importance of 99mTc-DMSA renal SPECT for the early diagnosis of acute pyelonephritis (APN) in patients under 3 yr of age. METHODS: Twenty-seven children under 3 yr of age, with clinical and/or laboratory suspicion of APN, were investigated. All 99mTc-DMSA renal SPECT and planar images and voiding cystoureterogram (VCUG) were obtained within 3 days of hospitalization. RESULTS: In the first examination, renal cortical defects were detected in 23 patients (42 kidneys) with SPECT and in 9 patients (11 kidneys) with planar scintigraphy. One year after treatment, constant renal cortical lesions were observed in 11 patients (14 kidneys) with SPECT and 4 patients (4 kidneys) with planar scintigraphy. The high grades of vesicoureteral reflux (VUR) (grade >or= 3) correlate better with APN diagnosed by SPECT (34 kidneys) than by planar scintigraphy (8 kidneys). Multiple renal cortical defects (number of lesions >or= 4) were only seen in patients under 1.5 yr old and none of those with a negative 99mTc-DMSA renal SPECT had a positive 99mTc-DMSA renal planar scintigraphy at any time. There is a significant difference (p < 0.05) between the diagnostic ability of these two methods of examination. CONCLUSION: Our results suggest that 99mTc-DMSA renal SPECT should be used, where possible, instead of planar DMSA in routine examination of children with clinical suspicion of APN, especially for those under 3 yr of age.

Strategies for development of combination vaccines.

BACKGROUND: The increasing complexity of the recommended childhood immunization schedule has resulted in the need for combination vaccines. METHODS: Through an extensive review of the current literature, various strategies and issues related to the development of combination vaccines are discussed. RESULTS: Issues that should be considered when combining vaccine components include the current childhood immunization schedule, compatibility of components, availability of antigens for targeted diseases, safety, efficacy, immunogenicity and route of delivery. When choosing an appropriate combination of antigen(s)/serotype(s) for a global or national formulation, careful consideration must be made when selecting serotypes to combine depending on the market or area of use. It is important to know that potential interactions can involve other components of the vaccines, including buffers, adjuvants and preservatives. The Food and Drug Administration requires that the combination not only have immunogenicity comparable with those of the component vaccines, but that its safety profile be comparable with the most reactogenic component. The Food and Drug Administration also recommends that a test of noninferiority be performed, such that the combination performs similarly to the separate components with regard to antibody titers. CONCLUSIONS: Combination vaccines are critical to the success of vaccination programs, and each new combination must be carefully studied to ensure comparable safety and immunogenicity of the individual components.

Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants.

INTRODUCTION: The objectives of this study were to evaluate the safety and immunogenicity of a new combination vaccine (DTaP-HB-IPV) containing diphtheria, tetanus, acellular pertussis and hepatitis B (HB) and a new inactivated poliovirus vaccine (IPV) manufactured by GlaxoSmithKline (GSK). This vaccine was given in an all IPV or sequential IPV and oral polio vaccine (OPV) schedule. Another combination vaccine, DTaP-HB (GSK), was similarly evaluated given with OPV or IPV. METHODS: Four hundred infants were randomized into one of four study groups and immunized at 2, 4 and 6 months of age. Group A received three doses of DTaP-HB-IPV; Group B received DTaP-HB-IPV at 2 and 4 months and DTaP-HB with OPV (Orimune) at 6 months; Group C received three doses of DTaP-HB with licensed IPV (IPOL) administered separately; Group D received separate doses of OPV, DTaP (Infanrix; GSK) and HB (Engerix; GSK). All subjects received conjugate Haemophilus influenzae type b vaccine (Hib) (OmniHIB) at 2, 4 and 6 months of age given at a separate injection site. Subjects who returned at 12 to 18 months of age (229) received booster immunization with DTaP and Hib. Safety was evaluated after each vaccine dose. Blood was drawn before the first dose and one month after the third dose as well as before and after the booster dose. RESULTS: There were no vaccine-related serious adverse events in any group after any vaccine dose. Minor systemic and local adverse events were also not significantly different among the four groups after any dose. There were no differences in the immune response rates for Hib, HB, polio (types 1, 2 and 3), diphtheria, tetanus or pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) among groups, although there were some quantitative differences in specific antibody titers among groups. DTaP-HB-IPV and DTaP-HB combination vaccines had safety and immunogenicity equivalent to those of standard individually administered vaccines. The new IPV was not inferior to IPOL. CONCLUSION: Use of the pentavalent combination vaccine would greatly reduce the number of required injections during the first 2 years of life, thereby simplifying the immunization schedule, enhancing compliance and facilitating acceptance of additional injections engendered by introduction of newer vaccines.

Diagnosis of vasculogenic impotence: combination of penile xenon-133 washout and papaverine tests.

The present study evaluates both penile xenon-133 washout (XWT) and papaverine tests (PT) in the diagnosis of vasculogenic impotence. XWT was accomplished by subcutaneous injection of xenon-133 (1-2 mCi in 0.1 mL saline solution) into the dorsal coronal prepuce. Abnormal XWT was suggested in patients whose clearance time (T1/2) was longer than 7.5 minutes and whose penile blood flow rate (Q) was less than 6 mL/100 g tissue/min. PT was done by intracavernous injection of papaverine (60 mg in 20 mL normal saline). Abnormal PT was indicated in patients whose onset of full erection was more than ten minutes after papaverine injection and whose duration of erection was less than one hour. Ten young and 11 older normal volunteers were examined with XWT only; all showed normal results. A total of 60 impotent patients were examined with both XWT and PT and were classified into four groups: in 2 patients (3.3%) both XWT and PT were normal (group I); in 8 (13.3%) XWT was abnormal and PT normal (group II); in 14 (23.3%) XWT was normal and PT abnormal (group III); and in 36 (60%) both XWT and PT were abnormal (group IV). On further examination with bilateral hypogastric arteriography in 10 XWT-abnormal patients and on surgical correction of abnormal curvature in 5 XWT-abnormal patients, all (100%) were proved to have penile arterial insufficiency. Erection cavernosography performed in 15 PT-abnormal patients confirmed penile venous insufficiency in 80 percent. We conclude both XWT and PT are simple and effective for evaluation of the penile arterial blood flow and venous competence, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of blood pressure differ in high and in low plasma renin groups.

It has been proposed that the aetiology, pathophysiological status, and effective treatment of hypertensives depends on concomitant plasma renin levels. Epidemiological data are scarce on the interrelations of plasma renin activity (PRA), BP and correlates of BP in the general population. Therefore, profiles of BP correlates were compared between low PRA groups and high PRA groups in a relatively healthy population of 321 Chinese government employees working in the Taipei area, in the summer of 1987. The characteristics of the two PRA groups were similar in body mass index, urinary sodium, chloride, calcium excretion and fasting parathyroid hormone. However, the high PRA group was younger, smoked more, and had a higher mean urinary potassium excretion. Fasting plasma glucose, uric acid, and creatinine levels were lower in the low PRA group. Positive relationships between BP and urinary sodium, chloride, potassium, calcium, plasma cholesterol, triglyceride, and glucose, independent of age and body mass index, were demonstrated in the low PRA group, where a volume expansion state may exist. However, in the high PRA state, uric acid, haemoglobin concentration, insulin and parathyroid hormone level were correlated more closely with BP than in the low PRA state. Further studies are needed to examine whether the differing associations between BP and risk factors in the high and low PRA groups reflect different compensatory mechanisms or aetiological factors.

An evaluation of the algorithms for determining local cerebral metabolic rates of glucose using positron emission tomography dynamic data.

Measurement of the local cerebral metabolic rate of glucose (LCMRGlc) and the individual rate constant parameters of the [(18 )F]2-fluoro-2-deoxy-D-glucose (FDG) model can provide a clearer understanding and insight to the physiological processes in the human brain, and a quicker and more accurate means of diagnosis in clinical applications. A systematic study using simulated and clinical tissue time activity data is presented to evaluate several existing and newly developed major algorithms used for determining LCMRGlc and the individual rate constants from positron emission tomography dynamic data. The computational and statistical properties of the autoradiographic approach, weighted and unweighted nonlinear least squares methods, Patlak graphic approach, weighted integration method, linear least squares and generalized linear least squares methods are investigated and discussed in this paper.

Detection of circulating cancer cells by nested reverse transcription-polymerase chain reaction of cytokeratin-19 (K19)--possible clinical significance in advanced gastric cancer.

Intermediate filament cytokeratin-19 (K19) protein is expressed in normal and malignant gastrointestinal epithelial cells, but not in peripheral blood (PB). Small amount of circulating gastric cancer cells can be detected by a sensitive nested reverse transcription-polymerase chain reaction (RTPCR) with primers specific for K19 mRNA. Thirty-four PB samples obtained from patients with inoperable/metastatic gastric cancer were examined. The mononuclear cell (MNC) fraction was collected by Ficoll centrifugation, and followed by total RNA extraction by acid guanidinium thiocyanate-phenol-chloroform method. RNA from 8 gastric cancer cell lines and the mononuclear cells of 33 healthy adults were used as positive and negative controls, respectively. DNA fragment of 774 bp amplified by the internal primers was found to be a highly reliable marker for K19 mRNA expression. The sensitivity of detection was between 1 and 10 cells/10(6) normal MNCs. The K19 transcripts were detected in 20.6% (7/34; 8-37%, 95% C.I.) of PB samples. None of the other pertinent clinicopathological features, including the disease extent and the histopathologic types of the tumors, were related to the expression of K19 in PB. All 34 patients had been treated by systemic chemotherapy. Among the 17 non-responders to chemotherapy, the survival of the 4 patients with detectable K19 was significantly shorter than that of 13 patients without detectable K19 in their circulating blood (p = 0.014). However, the survival impact of K19 was less significant in the other 17 patients whose tumors had responded to systemic chemotherapy. Of the whole group of patients, the median survival of the 7 and 27 patients with and without detectable K19 in their circulating blood was 1 and 3.5 months, respectively (p = 0.368). We concluded that detecting circulating cancer cells by K19 nested RT-PCR is associated with poor prognosis of gastric cancer, particularly in those patients who are not responsive to systemic chemotherapy.