Space-time database for standardization of adult magnetocardiogram-making standard MCG parameters

Background: The magnetocardiogram (MCG) is a promising medical tool for detecting and visualizing abnormal cardiac electrical activation in heart-disease patients. However, there is no large-scale MCG database of healthy subjects, and there is little knowledge of gender- and age-related influences on MCG data.
Methods and Results: We obtained MCG data from 869 subjects (554 men, 315 women) using a conventional 64-channel MCG system, which covers the whole heart. Electrocardiogram (ECG) data were also obtained; 464 people (268 men, 196 women) were identified as a normal group using ECG data. Time intervals (PQ, QRS, QT, and QTc), current distributions (maximum current vector (MCV), and the total current vector (TCV)) of MCG data of the 464 normal subjects were analyzed to obtain basic MCG parameters.
Although mean values of PQ and QRS intervals of the male subjects were slightly longer than those of the female subjects, no intervals were correlated with gender or age. The correlation between PQ intervals of ECG and those of MCG was better than the correlation between QRS and QT intervals of ECG and those of MCG. Both MCV and TCV angles were much smaller than the electrical-axis angle in ECG. Although TCVs of the QRS and T waves were stable, the women's mean T-wave-TCV angles significantly increased with age. The maximum amplitude of the P wave was about 1.7 pT, and the value of the QRS complex was about 20–25 pT. Moreover, the T-wave amplitude decreases with age.
Conclusion: The MCG standard space-time parameters determined here provide a normal range for MCG parameters.     

A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism

Simultaneous dual-isotope SPECT imaging with 201Tl and ¹²³I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion–metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, ^99mTc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of ^99mTc and ¹²³I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed ^99mTc-MIBI/¹²³I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between ^99mTc and ¹²³I. In the subsequent clinical study, ^99mTc-MIBI/¹²³I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by ^99mTc-MIBI and ¹²³I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional ²⁰¹TlCl/¹²³I-BMIPP dual-isotope imaging, the use of ^99mTc-MIBI instead of ²⁰¹TlCl improves image quality as well as lowers radiation exposure.     

Treatment of bedsores--combination of therapies depended the experimental design method

The treatment of bedsores is a particular problem in geriatric medicine. We selected standard drugs that may be effective for the decubitus ulcer, and investigated combination therapy to develop efficient treatment The subjects were 16 patients in whom the grade of the bedsore was evaluated as II to IV according to the Shea's depth classification. Treatment was performed while all patients were on air mats. We selected drugs and treatment methods based on the previously established experimental design of Taguchi. Based on this, we created and adapted 16 different component combination treatment programs in accordance with the L16 rectangular cross table. The following component factors were adopted: A: types of covering substances on the wound surface (Elase ointment, isodine sugar, isodine gel solcoseryl ointment); B: Isalopan powder; C: Spray of 10 ml physiological saline containing 500 microg of prostaglandin (concentration 0.005%); D: daily number of treatments; and F: presence or absence of tapping. We serially measured the wound surface area as an index of the speed of wound healing, and measured the interval (day) until the area decreased to one half of the original size (T1/2, half life). We analyzed data on one combination treatment each in 16 patients. Analysis of variance of the above factors showed significant F values for factors A, B, D and F. The contribution rates for factors A, B, D and F were 37.84%, 8.47%, 14.98% and 13.81%, respectively. The error term (e) was 16.37%. Optimal results were seen in the groups in which solcoseryl ointment had been applied twice a day. In this study, prostaglandin, which had been anticipated to be effective, did not show any effects. The error term (e) suggests the presence of other healing factors including individual differences. Concerning this point, it well be necessary to examine a larger number of patients in the future. With ointment treatment alone, without using an air mat, it was confirmed that bedsore area reduction was extremely unstable. Decompression of the affected part may be a basic prevention factor and essential treatment of bedsores.     

Epidemiological evidence that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated mean corpuscular volume in alcohol drinkers

BACKGROUND: Elevated mean corpuscular volume (MCV) is a traditional biological marker for alcohol abuse and alcoholism, but the underlying mechanism is unclear. Three recent epidemiologic studies consistently showed that MCV was elevated by alcohol drinking more markedly among individuals with genetically inactive aldehyde dehydrogenase-2 (ALDH2) (encoded by ALDH2*2 mutant allele) than those with active ALDH2 (encoded by ALDH2*1/2*1 genotype), suggesting that the elevated MCV was etiologically linked to acetaldehyde exposure. The purpose of the present study was to clarify further this relationship by examining the status of folate and vitamin B12. METHODS: The study participants were 159 men who were aged 40 to 69 years and randomly selected from a Japanese rural population. The genetic polymorphism of ALDH2 was determined by PCR-restriction fragment length polymorphism method; data on alcohol drinking and other lifestyles were collected using a structured questionnaire; serum concentrations of folate and vitamin B12 were measured using the protein competitive reaction method, and blood cell counts were measured by routine methods. A multiple linear regression model was used to analyze the data. RESULTS:: The relationship between alcohol drinking and serum folate concentration was significantly different between ALDH2 genotypes, indicating that the reduction of serum folate by alcohol drinking was more marked in men with ALDH2*1/2*2 than those with ALDH2*1/2*1. The relationship between alcohol drinking and elevated MCV was significantly stronger in men with ALDH2*1/2*2 than those with ALDH2*1/2*1 even after adjustment for serum folate and vitamin B12 concentrations. CONCLUSIONS: These findings indicate that acetaldehyde plays a significant role in the development of decreased serum folate concentration and elevated MCV by alcohol drinking.     

Combined effects of intraperitoneal administration of recombinant interleukin-2 and streptococcal preparation OK-432 in murine tumors

The combined effects of rIL-2 and OK-432 were investigated against a Meth-A tumor, a syngeneic tumor of inbred BALB/c mice. An analysis of the effector cells was also performed. The treatment resulted in an inhibition in vivo of tumor growth and increased survival of the Meth-A tumor-bearing mice. Splenic cells obtained from Meth-A inoculated mice which received combination therapy were not only NK-sensitive YAC-1 and LAK-sensitive EL-4 cells, but also NK-resistant Meth-A cells, as shown in a 4-h 51Cr-release assay. Syngeneic killer cell activity against Meth-A cells was abolished almost completely with anti-Thy 1.2 treatment and about 70% of the activity was abolished with anti-asialo GM1 treatment in a complement-dependent cytotoxic assay. It was not changed by the removal of macrophages and B cells from the splenic cells. Mice which survived for 60 days after the start of therapy rejected Meth-A inoculation when rechallenged, suggesting the establishment of a specific immunity. Combination therapy appeared to be beneficial against Meth-A cells and T-cells appeared to play a determining role in the treated Meth-A bearing mice. It was suggested that more than two populations of killer cells exist in the spleen treated with the combined therapy and they may have the same characteristics as activated T and NK cells with or without specific killer T-cells.     

Deficient in vitro anti-mycobacterial immunity despite successful long-term highly active antiretroviral therapy in HIV-infected patients with past history of tuberculosis infection or disease

We evaluated the anti-Mycobacterium tuberculosis (Mtb) immune responses of HIV patients after long-term successful HAART, presenting >500 TCD4+ cells/microl, undetectable viral load, and past history of tuberculosis infection (HIV+PPD+, n=14) or disease (HIV+CTB, n=17). Their lymphoproliferative and IFN-gamma responses were compared with those from HIV-uninfected controls either PPD+ (HIV-PPD+, n=17) or with past history of pulmonary tuberculosis (n=15). Most HIV-infected patients presented normal PHA responses while responses to the Mtb recombinant polypeptides ESAT-6 and Ag85B were markedly reduced. Responses to a whole Mtb lysate (S-Mtb) in HIV+PPD+ patients were lower than in HIV-PPD+ controls, while in HIV+CTB patients these responses were similar to that of past-tuberculosis controls. Comparison between the two HIV groups also suggested better S-Mtb responses in those cured from tuberculosis. Thus, while immune responses to single Mtb proteins are depressed even after successful HAART, reactivity to S-Mtb is high, specially in those cured from tuberculosis, possibly as a result of the survival of higher numbers of mycobacteria-specific T cell clones during the immunosuppression phase, which may afford sufficient protection against new Mtb challenges.     

An invasion-independent pathway of blood-borne metastasis: a new murine mammary tumor model

It is generally believed that active invasion by cancer cells is essential to the metastatic process. In this report, we describe a murine mammary tumor (MCH66) model of metastasis that does not require invasion into the vascular wall of both the primary tumor and the target organ, in this case, the lung. The process involves intravasation of tumor nests surrounded by sinusoidal blood vessels, followed by intravascular tumor growth in the lung, without penetration of the vascular wall during the process. Comparative studies using a nonmetastatic MCH66 clone (MCH66C8) and another highly invasive metastatic cell line (MCH416) suggested that high angiogenic activity and sinusoidal remodeling of tumor blood vessels were prerequisites for MCH66 metastasis. Differential cDNA analysis identified several genes that were overexpressed by MCH66, including genes for the angiogenesis factor pleiotrophin, and extracellular matrix-associated molecules that may modulate the microenvironment toward neovascularization. Our analyses suggest that tumor angiogenesis plays a role in the induction of invasion-independent metastasis. This model should prove useful in screening and development of new therapeutic agents for cancer metastasis.     

Diagnosis,treatment and maxillofacial rehabilitation in rhinocerebral mucormycosis patient: A case report and review of the literature

Mucormycosis is an aggressive, rare and opportunistic infectious disease, with a high mortality rate. Etiologic agents are filamentous fungi, and infection among humans normally occurs through spore inhalation. A 61-year-old male individual, presenting left eye amaurosis, dark epistaxis, hyperalgesia and malodor underwent clinical examination, which detected ulcerative lesion and wide bone exposure in the hard palate and alveolar ridge. Direct microbiological examination, microbiological culture and lesion biopsy were performed. Non-septate smooth fungal hyphae forming right angles with each other were observed through the direct microbiological examination. Microbiological culture revealed fast-growing fungal colonies with cottony texture, identified as Rhizopus sp. Histopathological examination exhibited necrosis areas, intense mononuclear inflammatory infiltrate and bulky hyphae, thus concluding the mucormycosis diagnosis. Amphotericin B antifungal therapy and surgical intervention were adopted as treatment. The patient was then rehabilitated with maxillofacial prosthesis, subsequently to the healing of the surgical wound.     

Effects of estrogen on susceptibility to oxidation of low-density and high-density lipoprotein in postmenopausal women

Objective: To investigate the effects of estrogen on the susceptibility to oxidation of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in postmenopausal women. Methods: A total of 23 postmenopausal women were treated with 0.625 mg of conjugated equine estrogen daily for 3 months. Blood samples were obtained before and after therapy. Plasma levels of total cholesterol and triglyceride and the concentrations of cholesterol, triglyceride, phospholipid in LDL and HDL were determined enzymatically and the levels of apolipoprotein A-I, A-II in HDL and apolipoprotein B in LDL were measured by turbidimetric immunoassay. The isolated LDL and HDL were incubated at 37°C for 24 h with CuSO₄ 5 μmol/l and the lipid peroxide concentration of LDL and HDL was measured. Results: Estrogen significantly reduced the plasma level of total cholesterol and significantly increased the plasma level of triglyceride. The LDL concentrations of cholesterol, phospholipid and apolipoprotein B were significantly decreased following estrogen therapy. The triglyceride level of LDL did not change significantly. The HDL concentrations of cholesterol, triglyceride, phospholipid and apolipoprotein A-I and A-II were all significantly elevated after estrogen therapy. Estrogen significantly inhibited the peroxidation of LDL at 50–2000 μg of LDL protein (14.17±4.17–11.49±1.42 nmol/200 μg of LDL protein, P<0.001) and of HDL (4.49±1.74–3.37±1.24 nmol/200 μg of HDL protein, P<0.03) induced by their incubation in the presence of CuSO₄. Conclusions: Estrogen inhibited the susceptibility of LDL and HDL to oxidative modification and favorably affected lipid metabolism by reducing the number of LDL particles and increasing the number of HDL particles in plasma that were resistant to oxidation.