The Effect of Total Blood Exchange with PHP Solution on Cardiac Xenotransplantation

Abstract: Prevention of hyperacute rejection is a difficult and unsolved problem in xenotransplantation. Natural antibodies and complement activation have been known to play an important role in the xenotransplantation between discordant species pairs. In the present study, total blood exchange (TBE) was performed with pyridox-alated-hemoglobin-polyoxyethylene conjugate (PHP) solution (Ajinomoto Co., Inc., Kawasaki, Japan) before cardiac xenotransplantation in order to remove the immunoglobulins and prolong xenograft survival time. Guinea pigs and rats were used as the discordant species combination for donor and recipient. Two groups were established: Group 1, untreated control (n = 8) and Group 2, TBT with PHP solution (n = 8). The exchange blood transfusion was carried out at the rate of 15–20 ml/h utilizing PHP solution using a blood pump. After the blood exchange was processed, hematocrit (Ht) levels dropped to 4 or 5%, and a cardiac xenotransplantation was performed within 24 h. The levels of serum IgA, IgM, and IgG were decreased to less than 25, 25, and 10% of the base line, respectively, after blood exchange. A mean xenograft survival time in Group 2 was prolonged to 472 ± 74 min and to 10.4 ± 1.8 min in Group 1 (p < 0.01). A titer of the anti-guinea pig lymphocytotoxic antibody in rat serum was decreased to almost nil. The data from this study suggest that total blood exchange with PHP solution may be useful in preoperative removal of xenograft antibodies in xenotransplantation.     

Increased procollagen III production in patients with kidney disease

Measurements of elevated procollagen III peptide (PIIIP) levels are used to monitor fibrosing activity in hepatic and various other diseases. Elevated PIIIP levels have also been reported in renal failure patients without such diseases. Therefore, the serum levels and renal clearance of PIIIP were investigated in 17 healthy volunteers and 100 patients with different types of acute (n = 15) and chronic (n = 85) kidney disease. PIIIP was measured by conventional and Fab radioimmunoassays. Median PIIIP levels in serum (18, range 5-55 ng/ml) and urine (34, range 1-110 micrograms/day) were significantly higher in kidney patients than serum (9, range 6-14 ng/ml) and urine levels (17, range 6-24 micrograms/day) in normal volunteers (p = 0.01). No significant differences (Kruskal-Wallis H test) were found, however, within the different kidney disease groups (acute, chronic/glomerulonephritis, interstitial nephritis). Median renal clearance of PIIIP-related peptides in kidney patients (1.5, range 0.5-2.4 ml/min) did not differ significantly (Wilcoxon U test) from that in normal volunteers (1.3, range 0.4-2.2 ml/min). These findings indicate that PIIIP elimination does not depend on renal function. PIIIP-related peptides in serum and urine, however, increase with renal failure irrespective of the activity or type of renal disease. This can be explained most probably by enhanced turnover of collagen type III by the affected kidney itself.     

Cutaneous eruption with or without ocular complications in patients with herpes zoster involving the trigeminal nerve

We examined 62 patients with acute herpes zoster involving the trigeminal nerve; 13 had eruptions only and 49 (51 eyes) had eruptions with ocular complications. Bilateral involvement was found in two patients. The frequency of the disease appeared to increase with age, and the disease was least active in November. Patients with eruptions only demonstrated affected areas along the first, second, and/or third divisions of the trigeminal nerve. Ocular complications occurred in patients who had eruptions along the first and/or second divisions of the nerve, and they were usually noted in patients with eruptions on the tip and one side of the node. The ocular complications and associated systemic conditions varied.     

Cytokines in bronchoalveolar lavage fluid in patients with high altitude pulmonary oedema at moderate altitude in Japan.

BACKGROUND: The precise mechanism of high altitude pulmonary oedema (HAPE) remains unclear. The purpose of this study was to evaluate the role of cytokines and P-selectin in the development of HAPE which occurred at moderate altitude in Japan. METHODS: The following cellular and biochemical markers and chemotactic cytokines were measured in the bronchoalveolar (BAL) fluid from four patients with HAPE at 2857-3180 m in the Japanese Alps: total proteins, albumin, lactate dehydrogenase (LDH), and interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (ra), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-alpha, and the soluble form of P-selectin. RESULTS: At admission there were significant increases in the levels of total cells, especially macrophages and neutrophils, total protein, albumin and LDH when compared with 13 healthy individuals. Furthermore, the levels of IL-1 beta, IL-6, IL-8, and TNF-alpha were also considerably increased but returned quickly to the normal ranges or were not detected after recovery. The levels of IL-1 alpha, IL-10, and P-selectin did not change. CONCLUSIONS: These results suggest that an inflammatory process almost identical with acute respiratory distress syndrome (ARDS) may occur in HAPE, but that these changes are transient and are not associated with any increase in P-selectin levels in the BAL fluid.     

Non-ketotic hyperglycinaemia due to a deficiency of T-protein in the glycine cleavage system in liver and brain

Non-ketotic hyperglycinaemia was diagnosed in a girl at 3 weeks of age because of the typical clinical presentation, the elevated glycine concentration in urine, plasma and especially in cerebrospinal fluid and the normal profile of organic acids in urine. An EEG showed the typical burst suppression pattern. Therapeutic approaches with either pyridoxine (50 mg d-1) alone or in combination with N5-formyltetrahydrofolate (3 X 3 mg d-1) or with strychnine (0.3 mg per kg body weight) did not result in improvement. In postmortem liver and brain of the patient the overall activity of the glycine cleavage system was deficient; examination of the activity of the individual components of the glycine cleavage system in the tissues revealed that the activity of the T-protein was undetectable, whereas that of the other components and of lipoamide dehydrogenase was normal.     

Effects of chlorpromazine-pretreated melanin on lysosomal acid phosphatase and N-acetyl-beta-D-glucosaminidase in bovine ciliary body and iris in vitro

We studied biochemically the effect of chlorpromazine-pretreated melanin on lysosomal enzyme activities in the bovine ciliary body and iris in vitro. Melanin was prepared from the bovine ciliary body and iris by acid treatment. Acid phosphatase and N-acetyl-beta-D-glucosaminidase of the ciliary body and iris were used as lysosomal marker enzymes. After the enzyme solution was incubated with melanin, enzyme activity was reduced and protein content in the supernatant was decreased. When melanin was pretreated with chlorpromazine, both enzyme activity and protein content in the supernatant remained higher than after the incubation with melanin alone, depending on the concentration of chlorpromazine. Chlorpromazine itself seemed to have little effect on the acid phosphatase and N-acetyl-beta-D-glucosaminidase at the concentration used in the incubation mixture. The increased enzyme activity, therefore, may result from a loss of the enzyme affinity for melanin after chlorpromazine pretreatment. These findings were discussed with respect to the binding mechanism of lysosomal enzymes to melanin and possible effect of chlorpromazine on biochemical interaction between lysosomal enzymes and melanin in vivo.     

PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

Herpes zoster ophthalmicus complicated by hyphema and hemorrhagic glaucoma

We treated two patients with herpes zoster ophthalmicus in whom hyphema and hemorrhagic glaucoma occurred. Case 1 complained of facial skin eruption, and was given intravenous acyclovir for 7 days. Hyphema and high intraocular pressure occurred in the left eye 10 days after the onset of the skin eruption. Case 2 had severe pain and blisters on her face, and was given intravenous acyclovir for 7 days. An intracameral hemorrhage and glaucoma developed in the right eye 15 days after the onset of the skin lesion. Intravenous acyclovir may be necessary for longer than 7-day periods if the iridocyclitis remains.     

The significance of CA-50, SLX and ST-439 in lung cancer]

Serum levels of CA-50, SLX and ST-439 were measured in 213 patients with lung cancer (92 adenocarcinomas, 63 squamous cell carcinomas, 37 small cell carcinomas and 21 large cell carcinomas) and 87 patients with benign lung disease. The overall positive rates in patients with lung cancer were 12.8% for CA-50, 29.7% for SLX and 25.3% for ST-439. The positive rates for CA-50, SLX and ST-439 in adenocarcinoma patients were 22.8%, 42.4% and 38.0%, respectively. Of the patients with benign lung disease, 4.8% were false positive for CA-50, 15.3% for SLX and 3.6% for ST-439. In the patients with adenocarcinoma of the lung, the combination assay of CEA and ST-439 had a highly accurate rate (61.9%).     

Gyrate atrophy of the choroid and retina: 15 Japanese patients.

We examined 15 Japanese patients who had gyrate atrophy of the choroid and retina with hyperornithinaemia. Their visual acuities fell to 0.2 or worse in the second or third decade of life. Myopia developed late in the first decade, and the refractions decreased to -10 or -15 dioptres at age 20. Tunnel vision developed at approximately age 20. Our results suggested that the visual functions of Japanese patients were worse in the third decade or later than similarly affected Finnish patients.