Hypofractionated stereotactic radiotherapy with and without transarterial chemoembolization for small hepatocellular carcinoma not eligible for other ablation therapies: Preliminary results for efficacy and toxicity

Aim: To investigate the efficacy and toxicity of hypofractionated stereotactic radiotherapy for the treatment of patients presenting with hepatocellular carcinoma (HCC) in a single institutional setting. Methods: Sixteen patients who presented with solitary HCC, including two patients with a tumor thrombus of the portal veins, were treated with stereotactic radiotherapy with or without transarterial chemoembolization. The criteria for stereotactic radiotherapy were existence of technical difficulties for other ablation therapies, inoperable disease or refusal to undergo surgery, tumor staged as Grade A or B according to the Child-Pugh classification, and solitary tumor distant from the gastrointestinal tract and kidney with a tumor volume <100 cm(3). In 14 of 16 patients, a total dose of 35- 50 Gy was delivered in 5-7 fractions over 5-9 days. Results: At the end of a mean follow-up of 612 days (median 611 days; range 244-994 days), all patients were alive. Eight of 16 patients had complete responses and seven others were judged as stable with lipiodol accumulation. In one patient, local recurrence developed after 489 days. Intrahepatic recurrences developed outside the treated volume in six patients and no extrahepatic metastases developed during follow-up. No serious treatment-related toxic manifestations developed. Conclusions: Stereotactic radiotherapy for HCC with or without transarterial chemoembolization is feasible therapy and provides good local control with a short treatment period. Stereotactic radiotherapy may be of clinical benefit in patients who are inoperable or for whom there are difficulties in other ablation therapies.     

A new method for measurement of right ventricular residual ratio using 121I-MAA

A new technique of precordial counting with 131I-MAA for measurement of right ventricular residual ratio (RVRR) was described. 131I-MAA was rapidly injected injected into the right ventricle at the time of right heart catheterization. The fraction of isotope discharged from this chamber per beat was determined with a crystal detector with tapered collimator which was pointed to the center of right ventricle. The radioisotope dilution curve was corrected by using the lung built up curve recorded by the other detector pointed to the lung field. Then, the right ventricular end-systolic volume (ESV) and the right ventricular end-diastolic volume (EDV) were calculated from the RVRR and stroke volume. In 6 patients with normal hemodynamics, the RVRR averaged 57.8 plus or minus 4.9%, the ESV 52.2 plus or minus 13.6 ml/M(2) and the EDV 89.4 plus or minus 15.1 ml/M(2). In 16 patients with heart diseases, the RVRR averaged 60.6 plus or minus 7.1%, the ESV 80.6 plus or minus 34.0 ml/M(2) and the EDV 127.2 plus or minus 43.6 ml/M(2). In 11 patients with chronic pulmonary diseases, the RVRR averaged 70.7 plus or minus 9.9%, the ESV 94.7 plus or minus 42.4 ml/M(2) and the EDV 133.0 plus or minus 46.5 ml/M(2). The RVRR in the last group increased significantly.     

Role of echocardiography in acute pulmonary embolism

The difficulty in making an accurate diagnosis of acute pulmonary embolism is well known. To clarify the role of echocardiography, including Doppler echocardiography, in acute pulmonary embolism, we examined hemodynamic and echocardiographic parameters in 9 patients with acute pulmonary embolism just before and after treatment with urokinase. As hemodynamic parameters normalized after treatment, echocardiographic parameters such as deformity index of the left ventricle (LV-DI), end-diastolic dimension of the right ventricle (RVDd), the left ventricle (LVDd), the inferior vena cava, and RVDd/LVDd all significantly changed toward normal. Highly significant correlations were found between the echocardiographic and hemodynamic parameters, the best of which was between the LV-DI and systolic pulmonary artery pressure (r = -0.885, p less than 0.001). Doppler echocardiography quantitatively evaluated the grade of tricuspid regurgitation, and accurately estimated systolic pulmonary artery pressure. We conclude that echocardiography, including Doppler echocardiography, sensitively reflects the right ventricular pressure and volume overload of acute pulmonary embolism, is quite useful for its diagnosis which is often difficult, and is suitable for noninvasive follow up of these patients.     

Descriptive patterns of severe chronic pulmonary hypertension by chest radiography

BACKGROUND: To find chest roentgenographic (CXR) features to help differentiate two representative diseases with severe chronic pulmonary hypertension (PH). STUDY SUBJECTS: Thirty-six consecutive patients with chronic thromboembolic PH (CTEPH), 38 with primary PH (PPH), and 37 with left heart disease and PH. METHODS: CXRs were reviewed about 6 features (left 2nd arc protrusion, right descending pulmonary artery diameter (rPAD), cardiothoracic ratio (CTR), right 2nd arc width, avascular area and pleural abnormality). Hemodynamic data and the degree of tricuspid regurgitation (TR) on echocardiography were compared with CXR findings. RESULTS: The diagnostic pattern of CTEPH was the presence of one of two findings, an avascular area or marked rPAD (>20mm) together with pleuritic change. The diagnostic pattern of PPH was one of the two features; without pleuritic abnormality, marked left 2nd arc protrusion (>10mm) or moderate left 2nd arc protrusion (5-10mm) with marked rPAD (<20mm). The sensitivity for the diagnosis of CTEPH among the three diseases was 78% and specificity was 92%. The sensitivity for the diagnosis of PPH was 45% and specificity was 88%. CTR and right 2nd arc width were related to the degree of TR in CTEPH and PPH. CONCLUSIONS: Characteristic roentgenographic findings can help differentiate two frequent diseases associated with chronic pulmonary hypertension and reflect the severity of disease.     

Skeletal Analysis of the Long Bone Abnormality (lbab/lbab) Mouse, A Novel Chondrodysplastic C-Type Natriuretic Peptide Mutant

Long bone abnormality (lbab/lbab) is a strain of dwarf mice. Recent studies revealed that the phenotype is caused by a spontaneous mutation in the Nppc gene, which encodes mouse C-type natriuretic peptide (CNP). In this study, we analyzed the chondrodysplastic skeletal phenotype of lbab/lbab mice. At birth, lbab/lbab mice are only slightly shorter than their wild-type littermates. Nevertheless, lbab/lbab mice do not undergo a growth spurt, and their final body and bone lengths are only ~60% of those of wild-type mice. Histological analysis revealed that the growth plate in lbab/lbab mice, especially the hypertrophic chondrocyte layer, was significantly thinner than in wild-type mice. Overexpression of CNP in the cartilage of lbab/lbab mice restored their thinned growth plate, followed by the complete rescue of their impaired endochondral bone growth. Furthermore, the bone volume in lbab/lbab mouse was severely decreased and was recovered by CNP overexpression. On the other hand, the thickness of the growth plate of lbab/+ mice was not different from that of wild-type mice; accordingly, impaired endochondral bone growth was not observed in lbab/+ mice. In organ culture experiments, tibial explants from fetal lbab/lbab mice were significantly shorter than those from lbab/+ mice and elongated by addition of 10⁻⁷ M CNP to the same extent as lbab/+ tibiae treated with the same dose of CNP. These results demonstrate that lbab/lbab is a novel mouse model of chondrodysplasia caused by insufficient CNP action on endochondral ossification.     

Convergence from the preoptic area and arcuate nucleus to the median eminence in acupuncture and nonacupuncture point stimulation analgesia

Lesion of the preoptic area (POA) or medial arcuate nucleus (M-HARN) abolished acupuncture analgesia (AA). Potentials in the median eminence (ME) evoked by stimulation of the acupuncture point (AP) were not affected by lesion of either the POA or M-HARN alone, but were abolished by concurrent lesion of both. No analgesia was produced by stimulation of the POA. Analgesia produced by stimulation of the M-HARN was abolished by lesion of the POA, and the abolished analgesia was restored by concurrent stimulation of the POA and M-HARN, hence POA and M-HARN outputs might converge in the ME to produce AA. Similar convergence from the anterior arcuate nucleus (A-HARN) and POA to the ME was observed in analgesia (NAA) produced by stimulation of a nonacupuncture point (NAP). Two pathways diverged from the lateral hypothalamus in the AA afferent pathway and two from the lateral periaqueductal central gray (L-PAG) in the NAA afferent pathway. POA potentials evoked by stimulation of the AP were reversed by naloxone, and those evoked by stimulation of the AP were reversed by dexamethasone. ACTH sensitive sites were found in both the L-PAG and the anterior hypothalamus.     

Serotonergic neurons in the brainstem modulate animal hypnosis

We previously found that the center of animal hypnosis production in the rabbit is located around the locus ceruleus and brachium conjunctivum (LC-BC) of the brainstem. The involvement of serotonergic neurons in this area of animal hypnosis was investigated by microinjection of serotonin into these regions. The duration of animal hypnosis (DAH) induced by inversion was diminished to about 65% of the controls by serotonin microinjection into the LC-BC and microinjection of methysergide prolonged the DAH to 3.2 times that of the controls. Flexor muscle contraction (CFM) of the upper extremities induced by electrical stimulation of the motor cortex was enhanced by serotonin. In normal rabbits, hard pressure on the ear base or the lumbar paravertebral area reduced CFM and this effect was partially antagonized by serotonin microinjected into the LC-BC. The results suggest that serotonergic neurons in the LC-BC modulate animal hypnosis.     

A new broad-spectrum aminoglycoside antibiotic complex, sporaricin. I. Fermentation, isolation and characterization.

Two new aminoglycoside antibiotics, sporaricins A (C17H35N5O5) and B (C15H32N4O4) produced by a rare actinomycetales, Saccharopolyspora hirsuta subsp. kobensis have been isolated by column chromatography on a cation-exchange resin. Sporaricin A is highly active against Gram-positive and Gram-negative bacteria including aminoglycoside-resistant strains.