Value of thallium-201 early reinjection for assessment of myocardial viability

To assess the efficacy of early reinjection forpredicting post intervention improvement in thallium-201 (Tl) uptake and regional wall motion, we reinjected a small dose of Tl following post-stress imaging and obtained reinjection early images (10 min after early reinjection) and reinjection delayed images (3 hr afterwards) in 40 patients who were referred to us for revascularization (group I). Twenty-nine patients in group I also underwent conventional stress-redistribution Tl scintigraphy (group II). Conventional stress-redistribution Tl scintigraphy was repeated after intervention. Contrast left ventriculography was performed before and after intervention and changes in regional wall motion were assessed in 22 of 40 patients. In group I, the predictive value for improvement and no improvement (the accuracy) of reinjection early images in perfusion was 83%, while that of reinjection delayed images was 91%. Furthermore, the accuracy of reinjection early images in regional wall motion was 80%, while it was 91% for reinjection delayed images. In group II, the accuracy in perfusion was 78% and the value in regional wall motion was 70%. Both accuracy in perfusion and in regional wall motion obtained from reinjection delayed images were significantly higher than the values in group II (p < 0.05). These data suggest that early reinjection is useful for predicting postintervention thallium uptake and regional wall motion.     

Identification of asynergic but viable myocardium in patients with chronic coronary artery disease by gated blood pool scintigraphy during isosorbide dinitrate and low-dose dobutamine infusion: Comparison with thallium-201 scintigraphy with reinjection

To evaluate the ability of low-dose dobutamine and isosorbite dinitrate (ISDN) gated blood pool scintigraphy (GBPS) and thallium SPECT with reinjection to identify viability in asynergic myocardium, both procedures were performed in 38 consecutive patients with chronic coronary artery disease and left ventricular dysfunction. Twenty-two of the 38 patients with successful revascularization were analyzed. GBPS was performed at the baseline and during continuous infusion of low dose dobutamine (5 μg/kg/min) and ISDN (2 μg/kg/min). Cine mode GBPS wall motion was scored from normal (0) to dyskinesis (4) semiquantitatively. Forty-seven of 110 segments with severe asynergy at the baseline were analyzed. Viability determined by GBPS was defined as wall motion score improvement by more than 1 grade. Thallium viability was defined as the segment with redistribution or fill in with severe initial perfusion defect. GBPS was 76.7% sensitive and 70.6% specific for predicting post vascularization wall motion improvement (p < 0.005). Of 47 segments with severe asynergy, concordance of judgement was obtained in 40 segments (85.1 %), and reversibility was correctly diagnosed in 34 of 40 patients (85.0%), but thallium with reinjection correctly identified tissue viability in 6 of 7 segments with discordance between 2 studies. These data suggest that most cases of reversible asynergy (hibernating myocardium) respond to ISDN and dobutamine, suggesting the possibility of predicting improvement by revascularization, although some underestimation of tissue viability remained to be resolved. Thallium with reinjection is superior to low-dose dobutamine + ISDN GBPS for the assessment of myocardial viability.     

Endocrine surgical pathology: lesson from pituitary cases that are discordant between clinical and pathologic diagnoses

There are a variety of clinicopathologic situations of pituitary lesions that could cause a discordance of diagnosis between clinicians and pathologists. This may be caused by confusion of terminology such as “nonfunctioning adenoma” and “null cell adenoma.” “Clinically nonfunctioning pituitary adenomas” comprise several pathologically different types of tumors that belong to one of three major cell lineages of adenohypophysial cell types. “Null cell adenoma” was originally defined by ultrastructural features but recently refers to immunonegative adenomas. Unique and unusual types of adenomas such as adenomas with “honeycomb Golgi” appearance and silent subtype 3 adenomas may cause a discordance of diagnosis. Because of mild elevation of prolactin levels, these adenomas are sometimes erroneously diagnosed as prolactinoma. Careful pathologic study with immunohistochemistry and electron microscopic examination, as well as communication between clinicians and pathologists, is vital. Confusion of terminology should be discussed. Awareness of rare disease entities is also required. Thorough analysis of individual cases with diagnostic inconsistency may provide a useful lesson for better understanding of endocrine diseases and for appropriate treatments.     

The influence of ageing and seasons on infantile eczema - a population-based cohort study of babies aged 4 months and 10 months]

BACKGROUND: This is probably the first report of a population study on infantile eczema performed for 12 months at two ages of 4 months and 10 months on the same infant group. METHODS: The Fujiidera Health Center services the health needs of 181,994 inhabitants of Habikino and Fujiidera cities. Between September 1990 and August 1991,1775 newborns were called for a health check-up performed twice a months when they reached 4 months of age. This was repeated for a year when the infants reached 10 months of age. A total of 1493 4-month old infants and 1264 10-month old infants were examined. An expert dermatologist joined this and performed a complete skin examination throughout the study. The eczematous skin changes were evaluated at 50 different points on the body and scored using an originally made chart. Scratch marks were also evaluated at each area. Based on the scores computed eczema was diagnosed when the total score crossed a threshold number. Based on this the examiner diagnoses were categorized as follows: Degree 1: no need to visit a doctor, Degree 2: visit to doctor required, Degree 3: treatment required. Gender was not considered. The data was analyzed by an originally made software using DEC-7000 computer. RESULTS: Of all the 4-month old infants examined 329 (22.0%) were initially diagnosed to have eczema while of all the 10-month old infants examined 268 (21.2%) were initially diagnosed to have eczema. Further, out of the 329 4-month old infants initially diagnosed with eczema, 228 were again examined when they were 10-months old. Of this sample; 123 (9.7%) infants showed continued symptoms of eczema and 165 (13.1%) infants no longer showed signs of eczema. In addition, out of the 976 4-month old infants initially diagnosed without eczema, 145 (11.5%) newly developed eczema at 10 months. Hence the cumulative diagnosis rate of eczema reached 34.3%. Meanwhile the monthly diagnosis number was significantly higher in Feb (OR 1.84, p=0.031) and significantly lower in Aug (OR 0.21, p<0.001) than the expected number calculated from monthly examination number and the annual diagnosis rate at 4 months. This observation was also the case at 10 months (Feb; OR 2.19, p=0.02, Aug; OR 0.36, p=0.015). The degree of eczema was significantly higher (p<0.001, Mann-Whitney's U test) at 4 months than 10 months. When this was seen monthly, degree 3 was most prevalent in February-March, while degree 2 was most prevalent in October-January for the 4-month olds. For the 10-month olds, both the degree 3 and degree 2 were quite low throughout the year and only degree 1 showed a monthly change similar to degree 2 plus degree 3 of the 4-month olds. CONCLUSION: We therefore conclude that eczematous skin manifestations of infantile eczema are easily changeable by age at less than 1 year and are strongly influenced by seasons.     

Absent inner dynein arms in a fetus with familial hydrocephalus-situs abnormality

We report a family in which a healthy, unrelated couple had a male fetus with bilateral ventriculomegaly, a normal liveborn girl, a hydatidiform molar pregnancy, a female fetus with ventriculomegaly and situs abnormalities, and a male fetus with hydrocephalus, a three-lobed left lung, and defective tracheal cilia with absent inner dynein arms and a single centriole. A mutation analysis of FOXJ1 and POLL in the last fetus with ciliary defect revealed no mutation within their coding regions. The presence of three affected fetuses of both sexes in a family with phenotypically normal parents suggests that the condition was inherited as an autosomal recessive trait. A thorough evaluation of the thoracic and abdominal situs is recommended before counseling a family of a child with hydrocephalus, because the recognition of situs defects may point to the diagnosis of primary ciliary defect and recurrence risk of 25% for siblings. This figure is much higher than the general risk of 1-2% for siblings of a patient with isolated hydrocephalus.     

Diurnal rhythm disorder of behavioral activity in SAMP1 mice is partially normalized by spontaneous wheel running

We examined the diurnal rhythms of food and water intake, spontaneous wheel running (SWR), and spontaneous motor activity (SMA) in the SAMP1 strain, a mouse model of accelerated senescence. Without SWR exercise, food, and water intake in the SAMP1 mice was significantly higher during the light (L)-phase of the light-darkness (LD) cycle than in the control SAMR1 strain. Additionally, SWR and SMA activity rhythms were split in SAMP1 mice, as demonstrated by the appearance of a secondary peak starting from the end of the dark (D)-phase. SWR exercise significantly increased the percentages of nocturnal food and water intake and SMA in the SAMP1 mice, although food and water intake did not reach the level of control SAMR1 mice. Thus, the disordered diurnal rhythms in SAMP1 mice can be normalized, even if only partially, by SWR exercise.     

Role for complement receptors (CD21/CD35) in the regulation of recombination activating gene expression in murine peripheral B cells

A population of peripheral B cells have been shown to express recombination activating gene products, RAG-1 and RAG-2, which are considered to be involved in revising the B cell antigen receptor (BCR) in the periphery. BCR engagement has been reported to turn off RAG expression in peripheral B cells, whereas the same treatment has an opposite effect on immature B cells in the bone marrow. In contrast to receptor editing that is involved in the removal of autoreactivity in immature B cells, it has been shown that secondary V(D)J rearrangement in peripheral B cells, termed receptor revision, contributes to affinity maturation of antibodies. Here, we show that RAG-2 expression in murine splenic B cells was abrogated by the coligation of BCR with complement receptors (CD21/CD35) much more efficiently than by the engagement of BCR alone. On the other hand, the same coligation augmented proliferation of anti-CD40-stimulated B cells. These findings suggest a crucial role for CD21/CD35 in directing the conservation or the revision of BCRs in peripheral B cells.     

Pericellular activation of proMMP-7 (promatrilysin-1) through interaction with CD151

Matrix metalloproteinase-7 (MMP-7) (also known as matrilysin-1) is secreted as a proenzyme (proMMP-7) and plays a key role in the degradation of various extracellular matrix (ECM) and non-ECM molecules after activation. To identify the binding proteins related to proMMP-7 activation, a human lung cDNA library was screened by yeast two-hybrid system using proMMP-7 as bait. We identified a candidate molecule CD151, which is a member of the transmembrane 4 superfamily. Complex formation of proMMP-7 with CD151 was demonstrated by immunoprecipitation of the molecules from CaR-1 cells, a human rectal carcinoma cell line, expressing both proMMP-7 and CD151, and CD151 stable transfectants incubated with proMMP-7. Yeast two-hybrid assays using deletion mutants of proMMP-7 and CD151 suggested an interaction between the propeptide of proMMP-7 and the COOH-terminal extracellular loop of CD151. The binding activity of (125)I-labeled proMMP-7 to CD151 on the cell membranes was shown with CD151 stable transfectants. Laser-scanning confocal microscopy demonstrated that proMMP-7 colocalizes with CD151 on the cell membranes of CD151 stable transfectants and CaR-1 cells. In situ zymography using crosslinked carboxymethylated transferrin, a substrate of MMP-7, demonstrated proteinase activity on and around CD151 stable transfectants and CaR-1 cells, while the activity was abolished by their treatment with MMP inhibitors, anti-MMP-7 antibody or anti-CD151 antibody. In human lung adenocarcinoma tissues, colocalization of MMP-7 and CD151 was demonstrated on the carcinoma cells. Metalloproteinase activity was present in these tissues and could be inhibited by antibodies to MMP-7 or CD151. These data demonstrate for the first time that proMMP-7 is captured and activated on the cell membranes through interaction with CD151, and suggest the possibility that similar to the MT1-MMP/MMP-2 system, MMP-7 is involved in the pericellular activation mechanism mediated by CD151, a crucial step in proteolysis on the cell membranes under various pathophysiological conditions including cancer invasion and metastasis.     

CD8+ T cells infiltrating into bile ducts in biliary atresia do not appear to function as cytotoxic T cells: a clinicopathological analysis

It is speculated that immune mechanisms are involved in bile duct damage in biliary atresia (BA), as in primary biliary cirrhosis (PBC). In BA, however, no reports have described the in situ distribution of cytotoxic T lymphocytes (CTLs) using specific markers, nor has the clinical association been clarified. The present study describes the immunohistochemical distribution of CD8+ T cells and the relevant markers [perforin, granzyme B, FasL (CD95L)] in 47 cases of BA operated upon at days 12-79. The results were compared with those of PBC. In BA, CD8+ T cells infiltrated bile ducts in a way similar to that observed in PBC. However, in sharp contrast to PBC, none of the inflammatory cells infiltrating into the bile ducts in BA expressed cytotoxic markers such as perforin, granzyme B, or Fas ligand (FasL). Clinical follow-up of patients with BA revealed that a greater degree of infiltration of bile ducts by CD8+ T cells is associated with better liver function. Taken together, these data suggest the absence of direct CTL activity against bile ducts in BA in the postnatal period.