Clinicopathologic findings of recurrent primary sclerosing cholangitis after orthotopic liver transplantation

Whether primary sclerosing cholangitis (PSC) occurs after orthotopic liver transplantation is controversial, largely because the pre-transplant diagnosis of PSC is based on nonspecific radiological and histological findings. We reviewed clinical, radiological, and histological records of 53 patients who underwent liver transplantation for PSC between 1985 and 1998. Three patients with patent hepatic arteries and no evidence of chronic rejection had radiological and histological findings that may have been due to recurrent PSC. Bile duct stricturing in these patients proved permanent and progressive and affected both the quality of life and graft survival. The first patient, who is 110 months after transplantation, has had repeated episodes of cholangitis for the last year. The second patient underwent excision of a strictured hepatic duct 45 months after transplantation and was ultimately retransplanted 95 months after initial transplantation. The third patient underwent left hemihepatectomy of an atrophied lobe 50 months after transplantation. Although the patient population assessed in this study is limited, putative recurrent PSC in the allografts has led either to graft loss or to clinically significant hepatobiliary complications of the graft. Received for publication on March 8, 1999; accepted on April 30, 1999     

Molecular basis of defective anion transport in L cells expressing recombinant forms of CFTR

Cystic fibrosis (CF) is caused by mutations in the gene encodinga chloride channel called the CF transmembrane conductance regulator(CFTR). A single mutation in this gene, deletion of three nucleotidesthat leads to the absence of phenylalanine 508 (i.e., F508),is found on 70% of all CF chromosomes. To explore the molecularmechanism(s) responsible for defective chloride transport inpatients with CF, we have studied the processing, localization,and function of wild type (W.T.), F508 and G551D CFTR (a GDmissense mutation at position 551) in retrovirus transducedL cells. Cell transduced with W.T. CFTR expressed a 170 kd CFTRprotein that was endoglycosidase H (Endo H) resistant, localizedto the plasma membrane, and generated a cAMP-mediated anionconductance (G_Cl) when stimulated with standard concentrationsof forskolin (5 µM), cpt cAMP (400 µM) and IBMX(100 µM). The G551D CFTR was indistinguishable from W.T.CFTR with respect to post-translational processing and localization,but it did not produce a cAMP-activated G_CI in response to thestandard stimulation cocktail. However, raising the IBMX concentrationto 4 mM produced Gc, in G551D expressing cells. Cells transducedwith F508 CFTR expressed an Endo H sensitive CFTR protein (140kd) that was found in a cytosolic, perinuclear location. Thesecells did not respond to the standard cocktail, but 20% of cellsincreased G_CI when the cocktail contained 4 mM IBMX. Incubationof cells at 26°C for 48 hours prior to analysis elicitedresponses in F508 expressing cells at low IBMX concentrations,but had no effect on the responses of cells expressing W.T.or G551D CFTR. The response of F508 to 26°C was associatedwith plasma membrane localization of CFTR protein. These resultssuggest that there are two mechanisms whereby CFTR mutationslead to loss of cAMP-responsive GCI. First, shown by G551D CFTR,the protein can be processed and targeted to the plasma membranecorrectly, but lack full responsiveness to stimulation by cAMP.Second, as examplified by F508 CFTR, a partially functionalprotein which is not targeted to its correct cellular locationcan also lead to loss of the cAMP, responsive G_CI.     

Prediction of facial nerve function after surgery for cerebellopontine angle tumors: use of a facial nerve stimulator and monitor

A series of 18 patients undergoing surgery for cerebellopontine angle tumors is reported. Patients were grouped according to size of tumor (0 to 2.5 cm, 11 cases; more than 2.5 cm, 7 cases). In all, the facial nerve was identified and conductance assessed by monitoring the facial electromyographic response to facial nerve stimulation. Postoperative facial nerve function was graded clinically after 3 months according to the House scale. Tumor removal was complete in all cases. In patients with tumors up to 2.5 cm the facial nerve was intact to visual inspection at the end of the procedure in all but one, where partial division was evident. In this group intraoperative facial nerve stimulation indicated electrical integrity in 8 of the 11 cases, all of which regained good facial nerve function postoperatively (House grades I and II). Nerve conduction was lost during the operation in the remaining three patients with small tumors; two subsequently developed a moderately severe (grade IV) dysfunction and the third, a total paralysis (grade VI). In the large (more than 2.5 cm) tumor group the facial nerve was anatomically intact in five of the seven cases, partially divided in one, and completely sectioned in the remaining case. Facial nerve stimulation indicated functional integrity in three patients, two of whom developed moderate (grade III) and the third a severe (grade V) dysfunction. In the other four cases nerve function could not be detected at operation; three of these developed a moderate facial nerve dysfunction (grade III/IV) and the final case a complete paralysis (grade VI). Intraoperative facial nerve monitoring appeared to predict eventual facial function accurately in the small tumor group, but did not predict facial nerve recovery reliably following surgery for larger tumors.     

Adenoid cystic carcinoma: factors influencing survival.

We have reviewed our experience with 264 patients treated for adenoid cystic carcinoma of salivary origin. This study updates a previous report from our hospital and includes all patients treated during a 30 year period who were eligible for a minimum follow-up of 10 years. The tumor arose in minor salivary (mucous) glands in two thirds of the patients; half had received treatment elsewhere, and both sexes were equally represented. Actuarial survival curves and "cure" rates calculated by the direct method confirm that clinical staging provides a reliable prognostic guide. We are unable to demonstrate that the microscopic appearance of the tumor exerts a predictable effect on treatment results. Although some patients lived for many years after resection despite local recurrence and distant metastases, prolonged survival was unusual in patients with stage 3 lesions, particularly in those with sinus or submaxillary gland primaries. Based on the site of origin of the tumor and its clinical stage, it is now possible to select which patients with adenoid cystic carcinoma have the most ominous prognosis and perhaps plan a more appropriate operation. More importantly, these data may help focus on the subpopulation at greatest risk, which is vital to the design of any prospective study to assess the value of adjunctive irradiation and chemotherapy.     

Behavioral evidence for supersensitivity after chronic bromocriptine administration

Behavioral evidence for tolerance and supersensitivity during and after chronic (30 day) administration of bromocriptine (BRC) or bromocriptine + L-dopa in mice was assessed by measuring wheel running (WR) behavior during and after chronic drug administration, and apomorphine- and methylphenidate-(MP-) induced stereotyped gnawing after termination of chronic injections. In both BRC and BRC +L-dopa groups, tolerance developed fairly quickly to the depressing effect of BRC on WR seen on day 1 of drug administration. Mice receiving BRC showed significant increases in WR by week 2 of chronic drug administration, which persisted for at least two days after the termination of chronic injections. During the first week after termination of chronic injections, low doses of both apomorphine and MP induced significantly more stereotyped gnawing in BRC and BRC + L-dopa mice than in the control mice or the mice treated with L-dopa alone. This behavioral evidence for dopaminergic supersensitivity after chronic BRC administration may have relevance for the clinical use of BRC in combination with L-dopa or other dopamine agonists.     

Fatal adenovirus pneumonia: Clinical and pathological features.

A review of autopsies of 107 young children with pneumonia showed that 15 children (14%) had adenovirus infections, the diagnosis being based on characteristic histopathological and ultrastructural features in the lungs. Eleven (73%) of the cases of adenovirus infection followed on measles infection, and it is suggested that some became infected with adenovirus after admission to hospital. A review of clinical aspects revealed no unique features. Histopathological examination of tissues showed a common picture of necrotising bronchopneumonia, with minor degrees of rental tubular damage, infiltrates of large mononuclear cells in spleen and nodes, and an absence of lymphoid germinal centres. On light microscopy, "rosette" and "smudge" cells were seen in these cases, and two patterns of virus particle distribution in infected cells were seen ultrastructurally. It is postulated that "smudge" cells contain numerous crystalline viral arrays.     

Cluster analysis of diffusion tensor magnetic resonance images in human head injury

OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic brain injury in humans, and its evolution in the acute phase, remain unresolved. This study aimed to characterize the topographical nature of the pathophysiological changes in human traumatic brain injury with diffusion tensor magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic resonance imaging data were acquired from five patients undergoing elective ventilation for management of traumatic focal contusion or hematomas. The diffusion tensor and the T2-weighted intensity were then computed for every voxel in the image data set for each patient. The topographical distribution of abnormalities in the trace of the diffusion tensor and T2-weighted images were characterized by cluster analysis. RESULTS: In four patients with technically satisfactory data, a narrow band of tissue was observed in the periphery of focal lesions, which was characterized by selective reduction in the trace of the diffusion tensor, without any associated increase in the T2-weighted signal intensity. CONCLUSION: This change is interpreted as indicating either a partial redistribution of water from the extra- to intracellular compartment, or a reduction in the diffusivity of water in the intracellular or cytosolic environment. These diffusion and T2-weighted characteristics are also found in early ischemic change, hence, such regions may represent potentially salvageable tissue at risk of permanent damage. The study illustrates the advantage of using information contained within the diffusion tensor in addition to more conventional imaging sequences.     

Pain and pain management in newborn infants: a survey of physicians and nurses

BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted.