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Biomedical subjects

M J Phillips

Publications and source records attributed to M J Phillips.

At least 109 records · Page 6Linked to original sources
PubMed1991

Neonatal hepatitis syndrome with paucity of interlobular bile ducts in cystic fibrosis.

A male infant presenting with neonatal hepatitis syndrome, characterized by conjugated hyperbilirubinemia and very mild liver function test abnormalities, at 2 weeks of age was found to have no excretion of radioisotope into the intestinal tract on hepatobiliary scan. Liver biopsy revealed severe interlobular bile duct paucity. Other features of Alagille's syndrome were not present; other conditions frequently associated with interlobular bile duct paucity were also excluded. Subsequently, the infant was found to have cystic fibrosis. Cystic fibrosis is thus another disease that may be associated with paucity of interlobular bile ducts presenting as neonatal hepatitis syndrome, and this represents a different pathogenesis of cholestatic jaundice in neonates with cystic fibrosis besides those previously recognized.

Alkaline Phosphatase↗
PubMed1991

Correlation of donor nutritional status with sinusoidal lining cell viability and liver function in the rat.

We have demonstrated that the sinusoidal lining cell injury sustained by rat liver allografts during hypothermic storage is a critical determinant of graft viability. The present study was designed to examine the effect of donor nutritional status on hepatic microcirculation and graft function. Rat livers from four nutritional groups (group I, fasted; group II, fed; group III, intraperitoneal glucose; and group IV, fed plus intraperitoneal glucose) were excised and stored for 24 hr in Marshall's isotonic citrate solution. Then the livers were perfused under anoxic conditions with trypan blue. The percentage of nonviable SLC in each group was 26.7 +/- 8.1, 24.9 +/- 7.9, 17.6 +/- 6.9, and 5.9 +/- 1.9 in groups I, II, III, and IV respectively; i.e., there was a significant improvement in SLC viability with nutritional repletion in group IV. Electron microscopy was performed on livers from groups I and IV following 30-hr preservation in University of Wisconsin solution and after 16-hr preservation in Marshall's isotonic citrate solution. Biopsies were taken at the end of storage and after 1 hr of reperfusion at 37 degrees C. At the end of preservation group IV livers contained glycogen and had much more normal liver ultrastructure than group I livers. After reperfusion there was partial recovery of normal SLC morphology in both groups and depletion of glycogen in group IV. Liver function was studied on the isolated perfused rat liver system at 37 degrees C following 30-hr storage in UW solution. Transaminase release into the perfusate was significantly lower in nutritionally repleted livers than in livers from fasted animals. A significant reduction in perfusate platelet count occurred only in livers from fasted animals. The results show that nutritional repletion can reduce the injury of cold preservation to both hepatocytes and endothelial cells and improve liver function in the postpreservation period.

Alanine Transaminase↗
PubMed1991

The interaction of acetylcholine and histamine on human bronchial smooth muscle contraction.

The interaction of histamine (Hist) and acetylcholine (ACh) on human isolated bronchial smooth muscle (HIBSM) contraction, and the influence of the epithelium, was assessed using HIBSM obtained from 15 patients undergoing thoracotomy. Cumulative concentration effect curves for ACh and Hist, together with combinations of equipotent concentrations of both agonists, were generated using both epithelium-intact and epithelium-denuded HIBSM. In epithelium-denuded HIBSM both ACh (p less than 0.05) and Hist (p less than 0.005) produced a significantly enhanced maximal response and a 2.1 fold increase in the potency of ACh (p less than 0.02, n = 13). When ACh and Hist were added simultaneously, in equipotent concentrations, to epithelium-intact HIBSM, a significantly less (p less than 0.0005, n = 13) than additive response occurred with only 60% of the predicted maximum response being observed. However, following epithelium removal, an additive interaction between the two agonists (n = 8) occurred. Using HIBSM from five of the original 15 patients, similar experiments were performed to determine the influence of the muscarinic receptor antagonist atropine (0.1 microM) and the H1 receptor antagonist mepyramine (10 microM). Both resulted in a significantly less than additive interaction (40-50% of predicted tensions). Similar experiments were also performed in the presence of the cyclo-oxygenase inhibitor indomethacin (5 microM) and these failed to reverse the inhibition observed in HIBSM contraction (n = 5). The inhibitory interaction between ACh and Hist appears to be epithelium dependent and is not mediated via the release of prostanoids. Thus, there appears to be a complex interaction between contractile agonists and the epithelium, which is not just a simple summation of the activation of individual receptors on HIBSM.

Acetylcholine↗
PubMed1991

Permeabilized hepatocyte couplets. Adenosine triphosphate-dependent bile canalicular contractions and a circumferential pericanalicular microfilament belt demonstrated.

The motility of bile canaliculi was examined in hepatocyte couplets permeabilized with palmitoyl lysophosphatidyl choline in a dosage regimen that drastically affected secretory function, yet maintained relative integrity of the cellular cytoskeleton. The permeabilized cells showed no exclusion of trypan blue, notable cytoplasmic organelle and membrane damage, and no uptake or secretion of either fluorescein diacetate or sodium fluorescein. However, bile canalicular structure remained relatively intact and actin and myosin were localized immunocytochemically in the pericanalicular region. Coincident with the administration of 1 mM ATP, 2 mM Mg2+, and 1 microM Ca2+, the canaliculi contracted with partial or complete luminal closure. ADP, AMP, or AMP-PCP could not be substituted for ATP. A dose-dependent relationship was shown between ATP concentration and canalicular contraction rate. The permeabilization procedure also provided enhanced visualization of pericanalicular microfilaments, believed to be actin filaments, and their organization into two layers: an inner membrane-associated network, and an outer filament bundle that inserted into belt junctions (zonulae adherentes). The organization of the microfilament belt of contiguous hepatocytes was such that it formed a circumferential band of microfilaments around the canaliculus. It is analogous to contractile filament belts found in the apical terminal web region of other epithelia. It was also observed that with canalicular luminal closure, there was a change in the organization of the pericanalicular microfilaments. It is concluded that in hepatocyte couplets, differential sensitivity of cell components to permeabilization can be achieved with palmitoyl lysophosphatidyl choline. In addition, the results provide evidence that the bile canaliculus has the capacity to be a contractile structure even in the absence of secretion, that canalicular contraction is ATP-dependent, and hence is a dynamic process.

Actin Cytoskeleton↗
PubMed1990

Phenobarbital hepatotoxicity in an 8-month-old infant.

Severe hepatotoxicity from phenobarbital occurred in an infant boy who had a complicated illness with chronic bilateral subdural hematomas and sepsis. Skin rash began after 2 weeks of treatment, and signs of hepatocellular failure developed 3 weeks after phenobarbital had been started. Signs of severe liver disease included elevated aminotransferases, conjugated hyperbilirubinemia, significant coagulopathy, hepatosplenomegaly and ascites. Other features of this adverse drug reaction were unremitting fever, leukocytosis with eosinophilia and atypical lymphocytosis, and proteinuria. Sepsis, viral hepatitis, and metabolic liver disease were excluded. The child was on no other medication and had been previously well. In-vitro rechallenge of the patient's lymphocytes with cytochrome P-450 generated metabolites of phenobarbital showed extensive cytotoxicity compared to control. These data support the hypothesis that a defect in drug detoxification was responsible for the child's susceptibility to this drug hepatotoxicity.

Carbamazepine↗
PubMed1990

Damaged goods: oral narratives of the experience of disability in American culture.

In a field project on oral narratives, I documented personal experience stories from 33 persons with visible, physical disabilities. These stories reveal informants' perceptions of how popular American notions about disability frame social interactions between disabled and nondisabled individuals, how such interactions affect the self-images of disabled persons, and how the predictability of such interactions constitutes a disabled experience that may be uniform across American culture.

Adult↗
PubMed1990

The effect of epithelium removal on human bronchial smooth muscle responsiveness to acetylcholine and histamine.

The respiratory epithelium produces a variety of inflammatory mediators which may be influencing the bronchial hyperreactivity observed in patients with asthma. Animal studies have demonstrated that removal of the epithelium from tracheal and bronchial smooth muscle causes enhanced responses to cholinergic agonists and histamine (Hist). In this study the effect of epithelium removal on human bronchial smooth muscle response to acetylcholine (ACh) and Hist was assessed. Bronchial smooth muscle was obtained fresh from the operating theatre from 12 patients undergoing thoracotomy. Cumulative concentration effect curves (CCEC) for Hist and ACh were generated for epithelium intact and epithelium denuded muscle strips. All CCEC's were performed in duplicate and all denuded strips were obtained from the same airway immediately adjacent to the intact strip. The mean (+/- SEM) maximum response for Hist for the intact strip was 8.6 +/- 1.1 (grams/gram wet weight) and 12.0 +/- 1.4 (grams/gram wet weight) for the denuded strip (p less than 0.05). For ACh the values were 9.3 +/- 1.3 (g/g wet weight and 14.3 +/- 1.8 (g/g wet weight), respectively (p less than 0.05). The pD2 (-log EC50) for ACh was increased two-fold following epithelium removal (p less than 0.05). For Hist there was a similar increase in pD2 but this did not reach statistical significance. Thus removal of the epithelium from human isolated bronchial smooth muscle appears to modulate responsiveness to ACh and Hist. This enhanced responsiveness consequent to epithelium loss may prove important with respect to the development of worsening asthma.

Acetylcholine↗
PubMed1990

Pneumothorax: treatment by small-lumen catheter aspiration.

To assess the efficacy of simple aspiration as a treatment for pneumothorax, 40 consecutive pneumothoraces (28 spontaneous, 12 iatrogenic, all estimated at greater than or equal to 20% collapse on visual inspection of the chest X-ray) in 38 symptomatic patients were treated initially by small-lumen catheter (SLC) aspiration. SLC aspiration avoided the need for large-lumen intercostal catheter (LIC) underwater drainage in 28 cases (70%)--20 of 28 spontaneous and eight of 12 iatrogenic pneumothoraces. Outcome was not predicted by clinical variables or pneumothorax size, whereas an initial aspirate volume of less than or equal to 4 L (n = 33) was predictable of success in 28 cases (85%). Minor local subcutaneous emphysema and vasovagal reactions were encountered infrequently but with similar frequency to LIC drainage. No episodes of re-expansion pulmonary oedema occurred. The results confirm previous reports of the efficacy of simple aspiration as a treatment for spontaneous or iatrogenic pneumothorax. Initial treatment by SLC aspiration is recommended for all but life-threatening presentations of pneumothorax. Although not encountered in this study, the potential risk of re-expansion pulmonary oedema suggests that patients should be observed closely for four hours after aspiration.

Adolescent↗
PubMed1990

The effects of nedocromil sodium on the response to grain dust in West Australian grain workers.

Seasonal grain workers in Western Australia who develop respiratory symptoms after exposure to grain dust develop concomitant changes in lung function and bronchial responsiveness to methacholine. The mechanisms underlying these changes are not known. A detailed study was undertaken of seasonal grain workers in Western Australia to evaluate the effect of nedocromil sodium (Fisons, United Kingdom) on these changes to see if they could be prevented by this drug. Forty seven subjects participated. Symptoms and forced expiratory volume in one second (FEV1) were recorded before the study and before, during, and after each working shift, and bronchial responsiveness to methacholine was measured at the beginning and end of the study. Twenty three subjects received nedocromil and 22 received a placebo in a double blind design; there was no difference in baseline characteristics between the two groups. At the end of the study, no differences were found between the nedocromil and placebo groups in the prevalence of symptoms or development of new symptoms during the study. The drug had no effect on changes in methacholine PD20 or FEV1. As in previous studies, new symptoms developing during the season were more common in atopic subjects and were associated with a fall in methacholine PD20. It is concluded that nedocromil has no effect on the development of new symptoms in grain workers. The mechanisms underlying these symptoms require further study.

Adolescent↗
PubMed1990

Liver cell dysplasia and early liver transplantation in hereditary tyrosinemia.

Two cases of hereditary tyrosinemia presented with ascites and coagulopathy in infancy. Both patients underwent liver transplantation at the age of 25 and 36 mo, respectively. Both cases had normal liver function 37 and 24 mo later. The native liver in each case showed mixed micro- and macronodular cirrhosis with hepatocellular dysplasia, including both the large and small cell varieties. One of the subjects had also shown dysplasia in a prior liver biopsy. We compared the hepatic morphology with that from two other cases from our autopsy files. One of these (a female, 9 mo old) showed dysplasia, and the other (her male sibling, 4 yr old) had a liver cell carcinoma with lung metastases. These observations confirm prior reports that neoplastic transformation occurs early in the natural history of hereditary tyrosinemia despite meticulous dietary management and other supportive treatment. With the detection of liver cell dysplasia, efforts should be intensified to find an appropriate donor. Liver transplantation cures the hepatic disease and should be performed before malignancy develops.

Amino Acid Metabolism, Inborn Errors↗
PubMed1990

Congenital abnormalities of the lymphatic system: a new clinical classification.

The numerous clinical presentations of congenital abnormalities of the lymphatic system in children and the confusing terminology used to describe their pathologic diagnoses impede the physician's understanding of the condition. The clinical classification based on the actual symptoms of the congenital problems we have presented here should help the physician identify the specific abnormality and a potential treatment. Future research should concentrate on the specific causes and the treatment of these congenital abnormalities.

Adolescent↗
PubMed1989

Incidence of leukaemia in young people in the vicinity of Hinkley Point nuclear power station, 1959-86.

The incidence of leukaemia and non-Hodgkin's lymphoma in young people (aged under 25) living in a predefined area around the nuclear power station at Hinkley Point, Somerset, was examined for the period 1959-86 by using cancer registry data. During the period since Hinley Point began operations--that is, 1964-86--there were 19 cases in the area compared with 10.4 expected from national rates, giving a standardised registration ratio of 1.82 (95% confidence interval 1.10 to 2.85). The incidence in the rest of Somerset was also high, however (standardised registration ratio 1.18; 95% confidence interval 0.98 to 1.41), and the high rate around Hinkley Point may simply have been reflecting the high local incidence (ratio of the two standardised registration ratio's 1.54; 95% confidence interval 0.90 to 2.52). Analysis of predetermined five year periods showed that the excess cases in the Hinkley Point area were concentrated in the 10 years 1964-73 after commissioning of the station, at a time when rates in the rest of Somerset were close to the national average. In particular the nine cases occurring in the five years 1969-73 were about four times the number expected from national rates (standardised registration ratio 3.96; 95% confidence interval 1.81 to 7.52). Rates in the Hinkley Point area after 1973 were fairly low, especially as compared with the rest of Somerset. In the five years 1959-63 (that is, before Hinkley Point was commissioned) rates throughout Somerset (including the Hinkley Point area) were higher than the national rate. These findings should be interpreted with caution, and further studies are required to test the plausibility of theories relating to radiation and viruses.

Adolescent↗
PubMed1989

Liver transplantation in children: the initial Toronto experience.

The Hospital for Sick Children's initial 2-year experience with pediatric liver transplantation is reviewed. Patients are divided into high- and low-risk groups according to certain criteria. The high-risk group includes patients under 10 kg in weight, those with extrahepatic biliary atresia (EHBA), those with portal vein atresia or thrombosis, and those in hepatic coma. All others were considered low risk. Twenty-nine patients were assessed for transplantation: 18 were transplanted and 6 (21% of total referred) died while on the waiting list. Eighteen patients received 23 transplants. Of the 18 recipients, nine had EHBA, four had fulminant hepatic failure, two had tyrosinemia, one had glycogen storage disease, one had Indian childhood cirrhosis, and one had idiopathic cirrhosis. Seven of the 13 patients in the high-risk group survived (55% survival) with 1 to 23 month follow-up. Survival was significantly higher (80%) in the low-risk group (P less than 0.05). Four patients were retransplanted and two survived. Early deaths occurred from prolonged warm ischemia, recurrent portal vein thrombosis, and brain death in a patient who had been transplanted in hepatic coma. Late deaths occurred from cytomegalovirus (CMV) disease (2 patients), acute rejection (1 patient), and myocardial infarction (1 patient). The incidence of primary nonfunction was 4.3% (1 of 23) and of arterial thrombosis was 13% (3 of 23). Survival in patients transplanted for EHBA (67%) was slightly higher than it was for the rest of the group, although not as good as it was in the low-risk group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Atresia↗
PubMed1989

Preoperative chemotherapy in 'unresectable' hepatoblastoma.

Chemotherapy was used to treat 11 children with hepatoblastoma that was judged to be unresectable because of tumor tissue in both lobes of the liver (eight patients) or because of size of the primary tumor (three patients). Three with bilobar involvement also had metastatic disease. Adriamycin was used in all patients. In nine, it was used in combination with cisplatin. A combination of other agents was used in four of these children. After two to six cycles (mean, 4 cycles), eight primary tumors exhibited marked response with greater than 50% reduction in size. Metastases disappeared in two patients. Complete resection of residual tumor was attempted in eight cases, and was successful in seven. One patient died at the time of surgery during an extended right hepatectomy. Two children had anaplastic hepatoblastomas that did not respond to chemotherapy, and the children died. One responder with giant cell hepatitis died from a severe coagulopathy and bleeding during chemotherapy before surgery. With preoperative chemotherapy, seven of 11 children with "unresectable" hepatoblastoma are now alive without disease 4 to 42 months following successful resection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Ia-positive dendritic cells form a tightly meshed network within the human airway epithelium.

In this report we have employed an alternative tissue-sectioning procedure which provides a plan view of intra-epithelial cell populations within the airway wall. Immunoperoxidase staining of such sections for class II MHC (Ia) antigen revealed the presence of a highly developed intra-epithelial network of Ia-positive dendritic cells, which was not evident employing conventional cross- or longitudinal tissue sections. This finding has important implications for the study of mechanisms underlying allergic and infectious diseases of the respiratory tract.

Dendritic Cells↗
PubMed1989

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.

Adolescent↗