Effect of tacrolimus and partial hepatectomy on transthyretin metabolism in rats

Liver transplantation, which serves as treatment of familial amyloidotic polyneuropathy (FAP), and domino liver transplantation, which utilizes resected livers from patients with FAP for treatment of liver diseases, may induce changes in transthyretin (TTR), a pathogenic FAP-related protein. To evaluate this possibility, we performed a 70% hepatectomy or administered tacrolimus to Dark Agouti (DA) rats for 7 days and then measured changes in liver TTR mRNA levels and changes in serum TTR concentrations. After hepatectomy, TTR mRNA levels decreased by 77%; at day 3, they returned to preoperative levels. Except for slightly elevated serum TTR concentrations 12 h after operation, serum TTR levels remained unchanged. Thus, partial hepatectomy did not influence serum TTR concentrations. After tacrolimus administration, TTR mRNA declined by 56% 12 h after the experiment started; however, after day 3, a rebound phenomenon occurred until day 7. Tacrolimus may facilitate serum TTR degradation, although production of TTR in the liver also increased. This finding -- that TTR, the source of FAP-inducing amyloid, did not increase after transplantation -- may help post-transplantation treatment of patients who have FAP and other liver diseases.     

Prosthetic valve endocarditis due to candida albicans treated successfully with medical treatment alone

Prosthetic valve endocarditis (PVE) caused by Candida species is associated with high morbidity and mortality. A combination of surgical resection and antifungal drug therapy is the golden standard for treatment, yet surgical intervention is not possible in all cases of Candida PVE. We report a case of PVE due to Candida albicans cured by medical treatment alone. This case suggests that, in some instances, Candida PVE can be managed medically with antifungal therapy. Such a conservative approach should be applied with caution and necessitates very close follow-up on a long-term basis.     

Clinical Course and Autopsy Findings of a Patient with Clival Chordoma Who Underwent Multiple Surgeries and Radiation during a 10-Year Period.

The management of clival chordoma remains problematic. We present the case of a 48-year-old woman with clival chordoma who underwent multiple surgeries and radiation therapy, including gamma knife stereotactic radiosurgery (GK-SRS), during a 10-year clinical course. The tumor was initially removed by gross total resection via the trans-sphenoidal approach, followed by external linac radiation therapy. The tumor recurred at the clivus 5 years after the initial operation. After repeated trans-sphenoidal removal of recurrent tumors, she twice underwent GK-SRS for a tumor remnant adjacent to the brainstem. Although this part of the tumor was controlled by GK-SRS, there was further tumor extension toward the sphenoid and maxillary sinuses. Ultimately, lower cranial nerve dysfunction developed due to tumor extension into the lower part of the clivus and the patient died of respiratory failure. Autopsy revealed the tumor to extend from the lower clivus to the bilateral middle fossae. The lower part of the tumor extended to the nasal cavity and to the posterior wall of the pharynx, resulting in compression of the upper pharyngeal region. The tumor around the jugular foramen compressed the lower cranial nerves bilaterally. Tumor cells did not, however, invade the intradural space microscopically. Although chordoma is not biologically malignant, this tumor can show massive extension with destruction of bony structures and extracranial invasion of connective tissues. Therefore, the optimal treatment strategy is to remove the tumor mass as extensively as possible, including normal bony structures and connective tissues surrounding the tumor, using skull base surgical techniques.     

An automated on-line method for simultaneous analysis of phenothiazines in human serum by high-performance liquid chromatography/sonic spray ionization mass spectrometry using backflush column switching

An automated on-line method for simultaneous analysis of five phenothiazine drugs by high-performance liquid chromatography (HPLC)/sonic spray ionization mass spectrometry (SSI-MS) has been established, using backflush column switching. A 400-μl portion of serum sample diluted 81-fold with distilled water was subjected to the on-line system. In the system, an Oasis HLB cartridge was used as the precolumn for extraction; large molecules such as proteins in serum were discarded by use of distilled water containing 0.1% formic acid as a mobile phase. After switching a valve, the analytes trapped in the precolumn were eluted in the backflush mode and separated by a Chromolith Performance RP-18e column, which is composed of C₁₈-bonded monolithic silica. The column effluents were then introduced into the SSI-MS. The present method provided successful separation and determination of six phenothiazines including an internal standard. Satisfactory linearities, reproducibility, and sensitivity were obtained at concentration levels that matched the toxic levels of phenothiazines. All drug peaks appeared within 18 min, and the system could be reequilibrated in only about 8 min for the next run. Because of the simplicity and rapidness of the method, it is likely to be useful in the fields of emergency medicine and forensic toxicology.     

Delayed onset massive oedema and deterioration in traumatic brain injury.

A 52-year-old man fell from standing and a computed tomography (CT) scan revealed traumatic intracerebral haematoma and subarachnoid haemorrhage in the temporal cortex. He was treated without surgery and discharged. On day 30 after the accident, he had no neurological deficit. On day 37 he complained of headache and urinary incontinence, and on day 39 he was hospitalized due to progressive neurological deterioration (reduced conciousness, dilated pupils, and left hemiplegia). A CT scan revealed a diffuse low-density in the right cerebral hemisphere with marked midline shift. Emergency decompressive craniectomy and right temporal lobectomy were performed. Angiography after surgery revealed moderate vasospasm in the right middle and anterior cerebral arteries. The patient remained severely disabled. Delayed onset neurological deterioration can be caused by brain oedema and vasospasm after traumatic brain injury, despite an intervening period of improvement.     

Missense mutation in exon 7 of the common gamma chain gene causes a moderate form of X-linked combined immunodeficiency.

Clinical and immunologic features of a recently recognized X-linked combined immunodeficiency disease (XCID) suggested that XCID and X-linked severe combined immunodeficiency (XSCID) might arise from different genetic defects. The recent discovery of mutations in the common gamma chain (gamma c) gene, a constituent of several cytokine receptors, in XSCID provided an opportunity to test directly whether a previously unrecognized mutation in this same gene was responsible for XCID. The status of X chromosome inactivation in blood leukocytes from obligate carriers of XCID was determined from the polymorphic, short tandem repeats (CAG), in the androgen receptor gene, which also contains a methylation-sensitive HpaII site. As in XSCID, X-chromosome inactivation in obligate carriers of XCID was nonrandom in T and B lymphocytes. In addition, X chromosome inactivation in PMNs was variable. Findings from this analysis prompted sequencing of the gamma c gene in this pedigree. A missense mutation in the region coding for the cytoplasmic portion of the gamma c gene was found in three affected males but not in a normal brother. Therefore, this point mutation in the gamma c gene leads to a less severe degree of deficiency in cellular and humoral immunity than that seen in XSCID.     

A comparison of ultrastructural changes on endomyocardial biopsy specimens obtained from patients with diabetes mellitus with and without hypertension

Summary The pathogenesis of diabetic cardiomyopathy is unknown. The synergistic, or enhanced, effect of hypertension on pathological changes in the heart of diabetic patients has been highly suspected. The purpose of this study was to evaluate the myocardial changes related to diabetes mellitus with and without hypertension, using biopsy specimens. We examined the ultrastructural changes in biopsy specimens of the endomyocardium obtained from 25 patients. They were divided into four groups: controls without hypertension or diabetes mellitus (n=6), and patient with hypertension (n=3), diabetes mellitus (n=8), and diabetes with hypertension (n=8). The diabetic patients showed nearly normal or mildly depressed systolic left ventricular function. Ultrastructural pictures were analyzed for thickening of the capillary basement membrane, presence of toluidine blue-positive materials (i.e., materials showing metachromasia) in the myocytes, size of myocytes, and interstitial fibrosis. The thickening of the capillary basement membrane, the accumulation of toluidine blue-positive materials, and interstitial fibrosis were all significantly greater in the patients with diabetes mellitus compared to the control subjects. The myocytes tended to be small (cell atrophy) in the diabetes group. Although these pathological changes in the heart were characteristic of diabetic patients, irrespective of the presence or absence of hypertension, the presence of hypertension increased the pathological changes of myocardial cells as well as abnormality in the capillary vessels in patients with diabetes mellitus. Alterations in the myocardial cells and capillaries, caused by diabetes mellitus, may lead to myocardial cell injury and interstitial fibrosis and, ultimately, to ventricular systolic and diastolic dysfunction, especially when the diabetes is accompanied by hypertension.     

Papillary adenoma of type 2 pneumocytes

A case of papillary adenoma of type 2 pneumocytes is reported. A 57-year-old man had an unusual coin lesion in the periphery of the right lung without any symptoms. When detected in a mass survey examination, it was approximately 1.5 cm in diameter, well circumscribed, and located in S4, involving the sixth-order bronchus of B4. Light-microscopic examination revealed cuboidal tumor cells arranged in a papillary pattern. Ultrastructurally, the cells had characteristic osmiophilic lamellar bodies. By immunoperoxidase staining, the tumor cells were shown to have intracytoplasmic surfactant apoproteins. The postoperative course was uneventful, and there is no evidence of disease 8 years later.