[Gastrointestinal hemorrhage induced by percussive ventilator in an infant with chronic lung disease complicated after surgery for corrected transposition of the great arteries].

A newborn patient (birth weight 2,332 g) with corrected transposition of the great arteries developed chronic lung disease due to a severe heart failure and post operative several complications. We applied intrapulmonary percussive ventilation (IPV) to the patient. IPV improved oxygenation concomitant with the improvement of respiratory condition and chest X-ray finding. However, the patient suffered from upper gastrointestinal bleeding 15 days after initiation of IPV therapy. The bleeding was healed several days after temporal termination of IPV, but recurred with resuming IPV therapy. The patient was irritable throughout the IPV therapy, and thus gastrointestinal bleeding of the patient could be due to stress induced by IPV therapy. IPV may be useful for the management of respiratory disturbance, often observed in low birth weight patients with congenital heart defects. However, gastrointestinal bleeding may occur and should be considered as a possible complication associated with IPV therapy.

Left ventricular outflow obstruction after Fontan procedure involving a patient with complete atrioventricular septal defects complicated by a small left ventricle.

We report a 1-year-old girl who developed ventricular outflow tract obstruction early after a Fontan operation, necessitating surgical relief using the Damus-Kaye-Stansel procedure. The patient had a complete atrioventricular septal defect complicated by a muscular ventricular septal defect (VSD) and a small left ventricle, a morphology that has not previously been reported in cases of systemic outflow tract obstruction after the Fontan procedure. Postoperative systemic outflow obstruction must be considered as a possible sequela following Fontan surgery in patients with an atrioventricular septal defect and a small left ventricle.

Trichilemmoma: an immunohistochemical study of cytokeratins.

BACKGROUND: The histogenesis of trichilemmoma remains unclear. OBJECTIVES: To clarify the histogenesis of trichilemmoma by evaluating its cytokeratin (CK) expression. METHODS: In three cases of trichilemmoma, CK expression was studied immunohistochemically using seven antikeratin antibodies against CK1, 10, 14-17 and 19, respectively. RESULTS: CK1 and CK10 were present in keratinizing ductal epithelium. CK14 was present in the whole layer. CK15 was present in suprabasal layers in two cases. CK16 was present in the suprabasal layer, but was absent in keratinizing ductal epithelium. CK17 was present in suprabasal layers and the sebaceous duct-like structure. CK19 was totally absent. CONCLUSIONS: These results showed that trichilemmoma may differentiate mainly towards two directions: infundibular keratinization and proliferation of the outer root sheath with undifferentiated and pluripotent characteristics.

Immunohistochemical study of cytokeratins in hidradenitis suppurativa (acne inversa).

In 14 cases of hidradenitis suppurativa, cytokeratin (CK) expression was studied immunohistochemically, using six antikeratin antibodies against CK1, CK10, CK14, CK16, CK17 and CK19, respectively. The draining sinus tract epithelium of hidradenitis suppurativa lesions was divided into three components: infundibular-like keratinized epithelium (type A), non-infundibular keratinized epithelium (type B), and non-keratinized epithelium (type C). In type A samples, CK17 (which is found in normal infundibulum) was not detected, suggesting fragility of this epithelial type. Keratin expression in types B and C epithelia was similar to that observed in the outer root sheath in normal hair follicles. Our results suggest that the draining sinus epithelium may possess characteristics of fragility, undifferentiation and hyperproliferation, as shown with CK expression.

Assessment of cardiovascular dynamics by pressure-area relations in pediatric patients with congenital heart disease.

OBJECTIVES: It is particularly useful to separately quantify the ventricular contractility and loading conditions for a better understanding of the cardiovascular dynamics in congenital heart disease, where abnormalities in chamber and loading properties may coexist. Furthermore, ventricular contractility and loading conditions may alter independently or simultaneously with disease progression and therapeutic intervention. The objectives of the present study were (1) to test whether ventricular pressure-area analysis can provide such quantitation among patients with various forms of congenital heart disease, (2) to reveal basal cardiovascular interaction in congenital heart disease by means of pressure-area analysis, and (3) to test the feasibility of this method in a simplified and less invasive form to further enhance its clinical value. METHODS: We constructed pressure-area loops during caval occlusion by using transthoracic echocardiographic automated border detection combined with ventricular pressure recordings in 59 pediatric patients with congenital heart disease and in 7 normal control subjects. RESULTS: Area measurements obtained by automated border detection were highly reproducible, and area changes reflected volume changes. The pressure-area data provided load-independent measures of contractility, which were consistently increased by use of dobutamine (P <.05). End-systolic and arterial elastance individually quantified simultaneous changes in ventricular contractility and loading with milrinone infusion and predicted net cardiac performance. The pressure-area analysis better characterized the ventricular contractile states under a variety of loading conditions in congenital heart disease, whereas predominant load dependence of conventional indices confounded them. Furthermore, pressure-area relations were reasonably estimated from a single beat and from aortic pressure data during abdominal compression. CONCLUSIONS: Pressure-area analysis should provide a useful modality with which to assess cardiovascular dynamics in pediatric patients with congenital heart disease in more detail and should thus help improve the management of patients with this disease.

Bone morphogenetic protein-2 and type IV collagen expression in psammoma body forming ovarian cancer.

Psammoma bodies (PBs), characterized as calco-spherules with concentric laminations, are common in serous tumors of the ovary. However, there is no agreements as to how the PBs are formed. Bone morphogenetic protein-2 (BMP-2) has recently been proposed to be involved in the calcification of tumor cells and recent electron microscopic studies demonstrated the presence of type IV collagen in PBs. Based on this evidence, we postulated a possibe role for BMP-2 and type IV collagen in the formation of PBs in ovarian cancer. We examined the expression of BMP-2 and typle IV collagen by immunohistochemistry and reverse transcription PCR (RT-PCR) in PBs-forming (NK-211) and -non-forming (SHIN-3, KF-1, A2780, KK-92, KOC-2S, SKOV-3, OMC-3, MN-1, EC, and KEN-3) ovarian cancer cell lines in vitro and in surgical specimens of serous adenocarcinoma (SA) with/without PBs and mucinous adenocarcinoma (MA) of the ovary. Cellular growth of cell lines was also evaluated by their doubling time in vitro. Transcripts for BMP-2 mRNA were detected by RT-PCR in all cell lines. By immunohistochemistry, BMP-2 protein expression was positive in 45% (5 out of 11) of cell lines. 36.4% (4 out of 11) were positive for type IV collagen. PBs-forming NK-211 was intensively positive for both BMP-2 and type IV collagen. In addition, NK-211 demonstrated extremely slow growth with a doubling time of 450 hours. In surgical specimens, BMP-2 vs. type IV collagen positivities in tumor cells were 100% (20 out of 20) vs. 40% (8 out of 20) in SA with PBs, 61.1% (11 out of 18) vs. 0% (0 out of 18) in SA without PBs and 75% (9 out of 12) vs. 0% (0 out of 12) in MA. In PBs themselves, 100% (20 out of 20) positivity for BMP-2 and 80% (16 out of 20) for type IV collagen was shown. These results raise the possibility that BMP-2 and type IV collagen-producing slow growing tumor cells form PBs in ovarian cancer.

[A case of very rare tuberculosis of the testis].

A 61-year old man visited our hospital with a painless swelling of right scrotal contents as the chief complaint. Transillumination test of the right scrotal contents was negative, and a quail's egg sized, elastic hard and smooth induration in the right testis was palpable. The laboratory data were normal except for slightly elevated E.S.R and CRP. Urine examination was normal. Although not only tumor marker, beta-hCG, AFP and LDH but also Plain lung X-ray, DIP and CT were normal, ultrasonography and MRI revealed a well-defined nodule in the right testis. Under the diagnosis of right testicular tumor, right high orchiectomy was performed. A yellowish white nodule of 2.5 cm in diameter was found in the slightly enlarged right testis. Pathologically, the patient was diagnosed as having tuberculotic granuloma with necrotic caseation. However, the epididymis was histologically normal. After operation, an antitubercular medication was started. Subsequently, E.S.R and CRP became normalized. At present, 12 months after surgery, the recurrence is not found. Tuberculosis of testis which shows no lesion in the epididymis is very rare, and ours is the first reported case in the Japanese literature. The importance of tuberculosis as a revival infection should be recognized in social circumstance in which tuberculosis is beginning to spread again.

Novel cell lines established from a human myxoid malignant fibrous histiocytoma arising in the uterus.

Two cell lines (Nara-H and Nara-F) with different phenotypes were established from a myxoid MFH of the uterus. In vitro, Nara-F grew in sheets showing a storiform arrangement and Nara-H in raised colonies. Although tumors generated in nude mice shared similar morphological features of abundant myxoid tumor in Nara-H and -F, the pleomorphic component was conspicuous in Nara-F. Both cell lines produced hyaluronic-acid but CD44 was expressed only in Nara-H. Estrogen receptor alpha (ER alpha) and progesterone receptor (PgR) were detected in Nara-H. Nara-F was positive for ER beta and PgR. Among hormonal agents, the response to the anti-estrogen tamoxifen was more sensitive than progesterone agents. This report illustrates the characteristics of these newly established cell lines, and presents the possibility of an adjuvant hormonal therapy for MFH.

Intraglomerular metastasis from pancreatic cancer.

Few case reports have shown the presence of metastatic tumor cells in renal glomeruli. We report one case with intraglomerular metastasis proved at renal biopsy. A 60-year-old man suffered from weight loss and fever of unknown origin. Urinalysis revealed proteinuria with cellular and granular casts. Because vasculitis was suspected, renal biopsy was performed. Presence of tumor cells occupying the glomerular capillary lumina was shown by means of light microscopy and electron microscopy. Laboratory findings revealed elevated leukocyte count (28.9 x 10(3)/mm(3)), serum granulocyte colony-stimulating factor (G-CSF) (77 pg/mL), and serum CA 19-9 (21,885 U/mL). The patient soon developed disseminated intravascular coagulation and died. Autopsy findings revealed pancreatic cancer showing positive staining for G-CSF and CA 19-9. Tumor cells in the glomerular capillary lumina showed positive staining for CA 19-9 and proliferating cell nuclear antigen (PCNA). These results suggest that the pancreatic tumor cells producing G-CSF were entrapped in the glomerular capillary lumina where they proliferated. This may have been the first step in renal metastasis.

Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines.

Diallyl disulfide (DADS) is an oil-soluble organosulfur compound found in garlic. The effect of synthetic DADS on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MDA-MB-231 and MKL-F) human breast cancer cell lines was examined. In an in vitro MTT assay, regardless of ER status, DADS at an IC(50) of 1.8-18.1 microM after 72 h incubation caused inhibition of growth in all four cell lines examined. Growth inhibition was due to apoptosis as seen by the appearance of a sub G1 fraction. In MDA-MB-231 cells, the apoptosis cascade comprised up-regulation of Bax protein (142%), down-regulation of Bcl-X(L) protein (38%) and activation of caspase-3 (438%) compared with controls. In an in vivo assay by orthotopic (right thoracic mammary fat pad) transplantation of KPL-1 cells in female nude mice, intraperitoneal injection of 1 or 2 mg DADS three times a week from the day of tumor cell inoculation until the end of the experiment (after 35 days) caused growth retardation and 43% reductions in primary tumor weight, respectively, compared with DADS-untreated mice without apparent side effects. Cell proliferation as evaluated by proliferating cell nuclear antigen (PCNA)-labeling in transplanted tumor of DADS-untreated mice was 59.6%, and 1 and 2 mg DADS-treated mice was 44.6 and 44.5%, respectively. In MDA-MB-231 cells, DADS antagonized the effect of linoleic acid (LA), a potent breast cancer cell stimulator (at DADS = 1.8 microM and LA > or = 6.5x10(2) microM concentration), and synergized the effect of eicosapentaenoic acid (EPA), a potent breast cancer cell suppressor (at DADS >3 x 10(-3) microM and EPA > 6.3 x 10(-1) microM concentration). Thus, DADS could be a promising anticancer agent for both hormone-dependent and -independent breast cancers, and may harmonize with polyunsaturated fatty acids known as modulators of breast cancer cell growth.

Resveratrol inhibits human breast cancer cell growth and may mitigate the effect of linoleic acid, a potent breast cancer cell stimulator.

Resveratrol is a naturally occurring product found in grapes and wine. The effect of synthetic resveratrol on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MKL-F) human breast cancer cell lines was examined. Resveratrol at low concentrations caused cell proliferation in ER-positive lines (KPL-1, < or = 22 microM; MCF-7, < or = 4 microM) whereas at high concentrations (> or = 44 microM) it caused suppression of cell growth in all three cell lines examined. Growth suppression was due to apoptosis as seen by the appearance of a sub-G1 fraction. The apoptosis cascade up-regulated Bax and Bak protein, down-regulated Bcl-xL protein, and activated caspase-3. Resveratrol (52-74 microM) antagonized the effect of linoleic acid, a potent breast cancer cell stimulator, and suppressed the growth of both ER-positive and -negative cell lines. Thus, resveratrol could be a promising anticancer agent for both hormone-dependent and hormone-independent breast cancers, and may mitigate the growth stimulatory effect of linoleic acid in the Western-style diet.

New diagnostic approach to intracystic lesions of the breast by fiberoptic ductoscopy.

Intracystic tumors of the breast are uncommon and, at the time of ultrasonography and aspiration cytology, it is difficult to distinguish cancer from a benign tumor. The Fiberoptic Ductoscopy System (FDS) is an emerging technique allowing direct visual access to the ductal system of the breast. FDS was inserted through the cannulae into the cavity and we observed the intracystic tumors (3 intracystic papillomas and 2 intracytsic papillary carcinomas). The appearance of the malignant tumors was irregular, rough-shaped and they tended to bleed. On the contrary, benign tumors had smooth surfaces without bleeding. Cytological findings showed malignant cells in one out of two breast cancer patients. In addition, in the immunohistochemical study of resected tumor tissues from 5 patients, we observed positive reactions with anti-ErbB-2 antibody in 2 intracystic papillary carcinomas. In contrast, none of the histologically confirmed benign lesions (3 intracystic papillomas) gave positive results. In conclusion, the use of FDS as a non-invasive technique may provide valuable information.

Immunohistochemical expression of bone morphogenetic protein-2 in pilomatricoma.

BACKGROUND: The mechanism of occurrence of calcification and ossification in pilomatricoma remains unclear. OBJECTIVES: To elucidate the pathogenesis of calcification and ossification in pilomatricoma we examined the role of bone morphogenetic protein (BMP)-2, which plays important parts in inducing ectopic bone formation both in vivo and in vitro. METHODS: Twenty cases of pilomatricoma were studied immunohistochemically using anti-BMP-2 monoclonal antibody. RESULTS: In normal skin, including hair follicles, there was no BMP-2 expression. In all pilomatricomas, BMP-2 was found exclusively in the cytoplasm of shadow cells but not in basophilic cells. In two cases of bone formation seen in pilomatricoma, osteoblasts in the periosteal area showed a strong positive reaction, while bone trabeculum (bone matrix) showed no reaction. CONCLUSIONS: Our findings indicate that shadow cells positive for BMP-2 may play an important part in generating bone formation in pilomatricoma.

Stent implantation for native coarctation of the aorta: lessons learned from a case involving a 17-year-old patient.

Recent studies have shown that stenting for coarctation of the aorta (CoA) may be an effective treatment modality for this disease. We report a case of stent repair of CoA in a 17-year-old patient. An incompletely expanded stent caused by a balloon rupture had been implanted in the femoral artery. Subsequent implantation for CoA was successfully achieved using a high-profile balloon catheter. Stent implantation may be an effective modality for CoA repair and may prove useful as an initial procedure for adolescents and adults with CoA. However, one must consider that incomplete expansion of a stent associated with dilatation balloon rupture can cause serious complications. The current case raises important issues that require further discussion to improve the results of this procedure.

Mucinous carcinoma of the breast with neuroendocrine differentiation.

A case of mucinous carcinoma of the breast with neuroendocrine differentiation in an 89-year-old woman is presented. The patient presented with a rapidly growing right breast mass, which she had had for 2-3 years. The tumor, 15 x 8 x 5 cm, was located mainly in the upper outer quadrant. Light microscopy revealed a pure mucinous carcinoma of type B. Neuroendocrine differentiation was demonstrated by Grimelius stain and chromogranin A, as well as the presence of neurosecretory granules. The breast cancer cells were of luminal origin and had dedifferentiated to attain neuroendocrine properties.

Retinal damage induced by cisplatin in neonatal rats and mice.

PURPOSE: The morphologic response of the retina at different neonatal ages to various doses of cis-platinum(II)diamminedichloride (cisplatin) was examined in rats and mice. METHODS: Cisplatin was given to rats at a dose of 1, 3 or 5 mg/kg at 0 days or 5 mg/kg at 7 or 14 days of age, and to mice at 0.5, 1.5, 3 or 6 mg/kg at 0 days or 6 mg/kg at 7 or 14 days of age, and the animals examined 12 and 24 hrs, and 3 and 7 days after the treatment. RESULTS: In both species, regardless of gender, with > or = 3 mg/kg cisplatin treatment (lethal dose) at day 0, retinal damage characterized by the appearance of aggregations of TUNEL-positive cells scattered in the undifferentiated neuroblastic layer was seen at 24 hrs, and led to rosette formation at day 3 and 7 (retinal dysplasia). At the ultrastructural level, neuroblastic cells showed condensation of chromatin and shrinkage of the cytoplasm, and rosettes encircled by an outer limiting membrane. Cell debris phagocytosed by pigment epithelial cells was seen. However, cisplatin at < 3 mg/kg in 0-day-old animals or at high dose in > or = 7-day-old animals caused no damage to the retina. CONCLUSIONS: A critical period (day 0) for the administration and a threshold dose (> or =3 mg/kg) of cisplatin in the development of retinal damage in rats and mice was seen. Although the cisplatin dose necessary to damage the retina caused a high incidence of mortality, it was below the human therapeutic dose.

Cataractogenesis in neonatal Sprague-Dawley rats by N-methyl-N-nitrosourea.

Cataract was induced by a single intraperitoneal injection of 100 mg/kg N-methyl-N-nitrosourea (MNU) to 0-, 5-, 10-, 15-, or 20-day-old male and female Sprague-Dawley rats. In day 0, 5, 10, and 15 MNU-treated rats, mature cataracts were constantly seen 7, 14, 14, and 30 days after dosing, respectively. In the day 20 MNU-treated rats, only subcapsular cataract was seen 30 days after dosing. Therefore, the rats exposed to MNU at an earlier age caused cataract more rapidly and severely. In the day 0 MNU-treated rats, 7-methyldeoxyguanosine DNA adduct was detected in the lens epithelial nuclei 12 hours after MNU dosing, followed by apoptosis, which was confirmed by morphology, by TUNEL signals, and by DNA ladder and peaked 3 days after MNU dosing. In the apoptosis cascade, upregulation of Bax, downregulation of Bcl-2, and increased CPP32 protease (caspase-3) activity were seen 12 hours after MNU dosing. Therefore, the pathogenesis of MNU-induced cataract was associated with DNA adduct formation in the lens epithelial cell nuclei leading to apoptosis by upregulation of Bax protein, downmodulation of Bcl-2 protein, and activation of caspase-3.