Bile acid profile as early indicator of allograft function during orthotopic liver transplantation

Orthotopic liver transplantation was performed in 20 pigs. Serum total bile acids (STBA) were determined and their profile compared with standard early function parameters: total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid. In phase I, the STBA level was 32.89 +/- 1.29 mumol/l. In phase II, STBA accumulated to 84.46 +/- 15.25 mumol/l (p less than 0.01), followed by hepatic clearance in phase III (63.61 +/- 9.71 mumol/1; NS). Between phase III and 6- and 12-hour samples, STBA decreased progressively, reaching values of 33.63 +/- 7.05 mumol/l at 24 h. AST was elevated in phases I, II, III, and at 6, 12 and 24 h (p less than 0.001), as was ALT (but with insignificant differences). Thus, STBA and their profile appear to be earlier and more specific indicators of early graft function than conventional parameters.     

Transient right-to-left shunting through a patent foramen ovale secondary to unilateral diaphragmatic paralysis.

A 57 year old patient presented with unilateral diaphragmatic paralysis and severe hypoxaemia secondary to transient right-to-left interatrial shunting through a patent foramen ovale. The final diagnosis was made because of the initial detection of a shunt while the patient was breathing 100% oxygen.     

Bone turnover in neonates: Changes of urinary excretion rate of collagen type I cross-linked peptides during the first days of life and influence of gestational age

New markers have been used to monitor the changes of bone turnover occurring during growth. Data on bone turnover rate during the perinatal period are, however, very scarce. In the present study we evaluated bone turnover rate, assessed by the measurement of urinary N-terminal telopeptide of type I collagen (NTx) concentrations, at different gestational ages, and we documented the trend of bone turnover rate occurring in the first days after birth. Urine samples were obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of diabetic mothers (IDMs). The first miction after birth was collected. Urine samples were also collected 24 and 48 h after birth. NTx was measured by an enzyme-linked immunosorbent assay (Osteomark®, Ostex International, Inc. Seattle, WA). The relationship between NTx at birth and all the other variables has been evaluated using multiple regression analysis. The changes of NTx excretion over time and the effect of the groups were studied by multivariate analysis of variance (MANOVA) for repeated measures. We found a remarkable association between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001). NTx concentrations showed a progressive decrement, reaching a nadir between the 38th and the 42nd week of gestation. The NTx concentrations changed significantly during the first 48 h of life in the three groups. Moreover, preterm infants had NTx excretion values at birth significantly higher than full term infants (p < 0.001), whereas NTx excretion rates of IDMs were not different from those of the other two groups of subjects. In conclusion, gestational age seems to be the major determinant of bone turnover in neonates; NTx excretion rate is higher before term, it slows in proximity of delivery, and it increases significantly during the first 48 h of life. Preterm infants have higher bone turnover rate than full term infants. NTx excretion rate of IDMs was comparable with those of the control subjects.     

Post-traumatic brain hypothermia reduces histopathological damage following concussive brain injury in the rat

The purposes of this study were (1) to document the histopathological consequences of moderate traumatic brain injury (TBI) in anesthetized Sprague-Dawley rats, and (2) to determine whether posttraumatic brain hypothermia (30°C) would protect histopathologically. Twenty-four hours prior to TBI, the fluid percussion interface was positioned over the right cerebral cortex. On the 2nd day, fasted rats were anesthetized with 70% nitrous oxide, 1% halothane, and 30% oxygen. Under controlled physiological conditions and normothermic brain temperature (37.5°C), rats were injured with a fluid percussion pulse ranging from 1.7 to 2.2 atmospheres. In one group, brain temperature was maintained at normothermic levels for 3 h after injury. In a second group, brain temperature was reduced to 30°C at 5 min post-trauma and maintained for 3 h. Three days after TBI, brains were perfusion-fixed for routine histopathological analysis. In the normothermic group, damage at the site of impact was seen in only one of nine rats. In contrast, all normothermic animals displayed necrotic neurons within ipsilateral cortical regions lateral and remote from the impact site. Intracerebral hemorrhagic contusions were present in all rats at the gray-white interface underlying the injured cortical areas. Selective neuronal necrosis was also present within the CA3 and CA4 hippocampal subsectors and thalamus. Post-traumatic brain hypothermia significantly reduced the overall sum of necrotic cortical neurons (519±122 vs 952±130, mean ±SE, P=0.03, Kruskal-Wallis test) as well as contusion volume (0.50±0.14 vs 2.14±0.71 mm³, P=0.004). These data document a consistent pattern of histopathological vulnerability following normothermic TBI and demonstrate hypothermic protection in the post-traumatic setting.Supported by USPHS Grants NS30291 and NS27127     

Matrix vesicles are enriched in metalloproteinases that degrade proteoglycans

Summary This study examined the presence of extracellular matrix processing enzymes in matrix vesicles produced by rat costochondral resting zone and growth zone chondrocytes in culture. Optimum procedures for the extraction of each enzyme activity were determined. Enzyme activity associated with chondrocyte plasma membrane microsomes was used for comparison. There was a differential distribution of the enzyme activities related to the cartilage zone from which the cells were isolated. Acid and neutral metalloproteinase (TIMP), plasminogen activator, and betaglucuronidase were highest in the growth zone chondrocyte (GC) membrane fractions when compared with matrix vesicles and plasma membranes isolated from resting zone chondrocyte (RC) cultures. There was a threefold enrichment of total and active acid metalloproteinase in GC matrix vesicles, whereas no enrichment in enzyme activity was observed in RC matrix vesicles. Total and active neutral metalloproteinase were similarly enriched twofold in GC matrix vesicles. TIMP, plasminogen activator, and betaglucuronidase activities were highest in the plasma membranes of both cell types. No collagenase, lysozyme, or hyaluronidase activity was found in any of the membrane fractions. The data indicate that matrix vesicles are selectively enriched in enzymes which degrade proteoglycans. The highest concentrations of these enzymes are found in matrix vesicles produced by growth zone chondrocytes, suggesting that this may be a mechanism by which the more differentiated cell modulates the matrix for calcification.     

The solid variant of adenoid cystic carcinoma of the cervix.

We studied seven examples of the solid variant of adenoid cystic carcinoma of the uterine cervix in postmenopausal women who presented with vaginal bleeding and a large ulcerated or polypoid cervical mass. The tumors lacked the characteristic cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae, and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas of necrosis in four. A characteristic feature was the production of abundant periodic acid-Schiff's procedure (PAS)-positive basement membrane material that was immunoreactive for collagen IV and that in some areas compressed tumor cells. Electron microscopy on three cases showed globules and cylinders of redundant basal lamina. The tumor cells were joined by desmosomes and contained bundles of tonofilaments. Material similar to basement membrane material appeared to be intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells were found. Four deaths were tumor related. Two patients are currently alive, but with local recurrence or metastases; another is alive and well 19 months after surgery. We believe that the solid variant of adenoid cystic carcinoma of the cervix is a distinctive neoplasm that should be separated from small cell carcinomas with or without endocrine features, adenoid basal cell carcinoma, and squamous cell carcinoma.     

Motor neuron disease and optic neuropathy after acute exposure to a methanol-containing solvent mixture.

A 34-years-old floor-layer developed optic neuropathy and motor neuron disease after being accidentally exposed to a solvent mixture containing methanol and other substances. Optic neuropathy is a complication of methanol poisoning, but the onset of a motor neuron disorder resembling amyotrophic lateral sclerosis after the exposure to these substances has not been previously described. The temporal onset of the clinical symptoms, biological plausibility, young age of the patient and absence of neurological disorders in the family history raises suspicion of a possible causative relationship.