Persistent left superior vena cava draining to left atrium with normal coronary sinus

In embryology, a persistent connection of the left superior vena cava to the left atrium rarely coexists with a coronary sinus. We herein report an unusual case of persistent left superior vena cava terminating in a left atrium with normal coronary sinus, which was revealed at the time of permanent pacemaker implantation after a second operation for recurrent left atrioventricular valve regurgitation. Because this anomaly had gone undiagnosed at the first operation, we were unable to diagnose it prior to the second operation, because the preoperative coronary angiogram clearly demonstrated a coronary sinus that was not dilated. We would have repaired the anomaly using a patch or other procedure had it been diagnosed before the second operation in order to prevent cyanosis or brain complications secondary to right-to-left shunting. One should always be on guard for this rare condition.     

Carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine in rats administered bis(2-hydroxypropyl)amine and sodium nitrite

The carcinogenic activity of endogenously synthesized N-nitrosobis(2-hydroxypropyl)amine(BHP) was investigated in male Wistar rats administered bis(2-hydroxypropyl)amine(BHPA) mixed in powder diet at a concentration of 1%, and sodiumnitrite (SN) dissolved in distilled water at concentrationsof 0.15 and 0.3%, for 94 weeks. Urinary excretion of BHP wasdetected in rats given 1% BHPA and 0.3% SN but not in the groupsreceiving either of these precursors alone. Nasal cavity, lung,esophagus, liver and urinary bladder tumors were found in animalstreated with combinations of 1% BHPA and 0.15 or 0.3% SN, suggestingthat the target organs of the endogenously synthesized BHP aresimilar to those affected when the carcinogen is administeredexogenously. The incidences of nasal cavity and lung tumorsreached 74 and 58% in rats given 1% BHPA and 0.3% SN, respectively.Tumors at sites other than target organs were only found atlevels similar to those previously reported for spontaneoustumors in male Wistars. The present results clearly indicatedthe tumor inducibility of a nhrosatable amine, BHA, throughan endogenous nitrosation by feeding to rats in conjunctionwith nitrite, and provide further suggestive evidence that endogenousnitrosations of environmental nitrosatable amines can be a potentialrisk factor in human cancer development.     

Renal Effects of Multiple Infusion of Pyridoxalated-Hemoglobin-Polyoxyethylene Conjugate (PHP) Solution in Dogs

Abstract: Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP), which is made from out-dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP-88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre- and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (C_H2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and C_H2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na⁺ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N-acetyl β-glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The result demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.     

Blockade of superoxide generation prevents high-affinity immunoglobulin E receptor-mediated release of allergic mediators by rat mast cell line and human basophils

BACKGROUND: Previous studies have shown that rat peritoneal mast cells and mast cell model rat basophilic leukaemia (RBL-2H3) cells generate intracellular reactive oxygen species (ROS) in response to antigen challenge. However, the physiological significance of the burst of ROS is poorly understood. OBJECTIVE: The present study was undertaken to investigate the role of superoxide anion in mediator release in rat and human cell systems. METHODS: RBL-2H3 cells were directly stimulated with anti-rat FcepsilonRI alpha-subunit monoclonal antibody (mAb). For the analysis of human cell system, leucocytes were isolated by dextran sedimentation from healthy volunteers or from patients, and challenged either with anti-human FcepsilonRI mAb or with the relevant antigens. Superoxide generation was determined by chemiluminescence-based methods. The releases of histamine and leukotrienes (LT)s were determined by enzyme-linked immunosorben assay (ELISA). RESULTS: Cross-linking of FcepsilonRI on RBL-2H3 cells or on human leucocytes from healthy donors by the anti-FcepsilonRI mAb resulted in a rapid generation of superoxide anion, as determined by chemiluminescence using superoxide-specific probes. Similarly, leucocytes from patients generated superoxide anion in response to the challenge with the relevant allergen but not with the irrelevant allergen. Furthermore, diphenyleneiodonium (DPI), a well-known inhibitor of flavoenzymes suppressed the superoxide generation and the release of histamine and LTC4 induced by the anti-FcepsilonRI mAb or by allergen in parallel. CONCLUSION: These results indicate that both RBL-2H3 cells and human basophils generate superoxide anion upon FcepsilonRI cross-linking either by antibody or by allergen challenge and that blockade of the generation prevents the release of allergic mediators. The findings strongly support the role of superoxide generation in the activation of mast cells and basophils under both physiological and pathological conditions. The findings suggest that drugs regulating the superoxide generation have potential therapeutic use for allergic disorders.     

LONG‐TERM OUTCOME OF ENDOSCOPIC BALLOON DILATION IN OBSTRUCTIVE GASTROINTESTINAL CROHN's DISEASE

Background: Gastrointestinal strictures are the most often and serious complication in Crohn's disease. Because of the frequent postoperative recurrence in Crohn's disease, endoscopic therapy of gastrointestinal stricture is one of the best therapeutic options. Method: The present study sets out the results from a prospective study of endoscopic dilation therapy on 48 Crohn's disease patients with severe gastrointestinal stenoses. All patients who could not undergo endoscopic balloon dilation therapy (EBD) were operated on. Results: Long‐term success was attained in 32 of the 48 patients; cumulative avoidance of surgery after EBD was 86% at one year and 71% at three. Second, the most hazardous factor was recurrent inflammation causing restenosis. Patients who had strictures with oral luminal dilatation and patients with frequent recurrence had a tendency to be operated on. As a complication, perforation occurred in two cases (3.3%). Conclusions: EBD therapy for Crohn's stricture in the gastrointestinal tract is recommended before surgical intervention.     

The effect of protein restriction on the severity and recovery from ischemic renal failure

The effects of chronic dietary protein restriction on ischemic renal failure were evaluated in rats subjected to 90 min of bilateral renal clamping. The rats were kept on either 20% casein (regular) diet or casein-free (protein-free) diet 10 days before and 21 days after renal injury. Rats on regular protein diet showed higher levels of BUN and serum creatinine and had a lower inulin clearance (microliter/min/100 g BW) than animals on protein-free diet (289 +/- 34 vs 582 +/- 103, p less than 0.05) 2 days after ischemia. However, the inulin clearance measured 21 days following ischemia was significantly higher in rats on regular diet (1468 +/- 181) than those maintained on protein-free diet after ischemia (560 +/- 167). When unilateral 90 min ischemia was performed in rats on regular diet, the postischemic kidneys showed an incomplete recovery of the inulin clearance (226 +/- 35) compared to the contralateral kidney (900 +/- 116), 21 days after ischemia; whereas in rats on a protein-free diet the inulin clearance averaged 106 +/- 17 in the postischemic kidney and 345 +/- 41 in the right kidney. When left renal ischemia and contralateral nephrectomy were performed, the inulin clearance was 1149 +/- 74 in rats on regular diet and 534 +/- 60 in rats on protein-free diet, 21 days following renal insult. These results suggest that protein restriction can play a protective role against renal ischemia in an initial phase, but it limits the late recovery from ischemia. The presence of a normal contralateral kidney inhibits the functional recovery of the postischemic kidney and a contralateral nephrectomy produces a compensatory functional hypertrophy of the postischemic kidney, even in rats on a protein-free diet.     

Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo.

Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl-nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5-fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells.     

Gallium scintigraphy in patients with adult T-cell leukemia lymphoma

Gallium scintigraphy was evaluated in 25 patients with adult T-cell leukemia lymphoma (ATLL). Anterior and posterior images were obtained at 72 h after administration of 3 mCi ⁶⁷Ga-citrate using a gamma camera (Maxi-Camera 400T, General Electric Co.) with a medium energy standard parallel hole collimator. Abnormally high accumulations were observed in 17 out of 25 cases (superficial lymph node, 8; hilar and mediastinal lymph node, 7; paraaortic lymph node, 2; lung, 9; liver, 1; bone, 1). There were 10 malignant lesions detected by ⁶⁷Ga scintigraphy in 9 out of 17 cases (superficial lymph node, 1; hilar and mediastinal lymph node, 6; paraaortic lymph node, 1; liver, 1; bone, 1). White blood cell count and serum LDH levels were raised in patients with abnormally high accumulations of ⁶⁷Ga. In conclusion, ⁶⁷Ga scintigraphy seemed to be a useful examination to detect malignant lesions in patients with ATLL.