Solitary necrotic nodule of the liver: A riddle that is difficult to answer

Solitary necrotic nodule of the liver is an unusual lesion that is often an incidental finding on abdominal imaging, intraoperative examination, or post mortem. Most reported cases of solitary necrotic nodule have been in males, and over three quarters of these lesions have occurred in the right lobe of the liver. Pathologically, solitary necrotic nodule is a benign lesion characterized by a completely necrotic core that is often partly calcified, surrounded by a dense hyalinized fibrous capsule containing elastin fibres. The ultrasound appearance of solitary necrotic nodule is usually of a “target” lesion with a hyperechoic center, while on CT scan they appear as non-enhancing hypodense lesions that are typical of metastatic adenocarcinoma or peripheral cholangiocarcinoma. The impression of malignancy is further enforced with the finding of necrotic cellular material on biopsy and the macroscopically hard and “gritty” nature of the nodules. Currently, permanent histopathology of solitary necrotic nodules is the only accurate method of diagnosis. However, solitary necrotic nodules are usually of a bilobed or lobulated shape that is unusual for malignant liver lesions, and they often lie in close proximity to hepatic inflow structures. Solitary necrotic nodule should be suspected in liver lesions with this configuration, location, and on a biopsy showing a large amount of necrosis.     

Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease.

Previous studies in the MPTP-lesioned primate model of Parkinson's disease have demonstrated that alpha(2) adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L-dopa-induced dyskinesia and, in the case of idazoxan, enhance the duration of anti-parkinsonian action of L-dopa. Here we describe a novel alpha(2) antagonist, fipamezole (JP-1730), which has high affinity at human alpha(2A) (K(i), 9.2 nM), alpha(2B) (17 nM), and alpha(2C) (55 nM) receptors. In functional assays, the potent antagonist properties of JP-1730 were demonstrated by its ability to reduce adrenaline-induced (35)S-GTPgammaS binding with K(B) values of 8.4 nM, 16 nM, 4.7 nM at human alpha(2A), alpha(2B), and alpha(2C) receptors, respectively. Assessment of the ability of JP-1730 to bind to a range of 30 other binding sites showed that JP-1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5-HT) transporter (IC(50) 100 nM to 1 microM). In the MPTP-lesioned marmoset, JP-1730 (10 mg/kg) significantly reduced L-dopa-induced dyskinesia without compromising the anti-parkinsonian action of L-dopa. The duration of action of the combination of L-dopa and JP-1730 (10 mg/kg) was 66% greater than that of L-dopa alone. These data suggest that JP-1730 is a potent alpha(2) adrenergic receptor antagonist with potential as an anti-dyskinetic agent in the treatment of Parkinson's disease.     

Mammalian wound repair environment does not permit skeletal muscle regeneration

Repair and regeneration are mutually exclusive responses to injury. Previous studies have shown that wound fluids promote proliferation, but not differentiation, of myoblasts in vitro. This study explored the ability of the repair environment within polyvinyl alcohol sponges to support cellular events of skeletal muscle regeneration in vivo. Neonatal rat L8 myoblasts were modified to express beta-galactosidase then inoculated into plain sponges or sponges containing minced muscle. Labeled myoblasts were found in myotubes within minced muscle. In contrast, myoblasts inoculated into sponges lacking muscle remained mononucleate. Occurrence of labeled myoblasts within myotubes, which required fusion, represents differentiation of inoculated myoblasts to participate in regeneration. Failure of myoblasts to form myotubes in sponges lacking muscle suggests that this wound repair environment cannot support morphologic differentiation of myoblasts. Although this repair environment can support the survival of myoblasts, it did not support myogenesis, an event necessary to complete skeletal muscle regeneration. Data from this study reinforce earlier studies in vitro and suggest that the properties attributed to wound fluids are inherent in the wound environment. Whether the inability of this environment to support myogenesis is the consequence of the absence of essential factors or the presence of inhibitors remains to be determined.     

NMR Microscopy of Single Neurons Using Spin Echo and Line Narrowed 2DFT Imaging

NMR microimages of single neural cells were acquired at 500 MHz using a conventional spin echo pulse sequence and a line-narrowing sequence that eliminates susceptibility effects. The data show that any contribution to the measured T₂ relaxation rate arising from diffusion in local field inhomogeneities using spin echo sequences at high fields and high spatial resolution is relatively small. We conclude that the measured T₂ difference between the nucleus and cytoplasm in these cells represents primarily a true T₂ relaxation effect arising from the interactions of water with macromolecules in the two compartments and does not result from microsusceptibility differences. These observations have implications regarding water compartmentation in single cells and the interpretation of the MR characteristics of tissues in vivo.     

Offene Synovektomie des Kniegelenks bei rheumatoider Arthritis

Operationsprinzip Obwohl sich weniger invasive Methoden der Synovektomie, wie zum Beispiel die radiochemische oder arthroskopische Vorgehensweise, zunehmender Beliebtheit erfreuen, bleibt die offene operative Behandlung einer schweren Synovialitis des Kniegelenks, selbst in weit fortgeschrittenen F?llen, die Methode der Wahl. Die Entfernung der chronisch-entzündlich ver?nderten Membrana synovialis scheint die Lokalsituation in der Mehrzahl der F?lle unter Kontrolle zu bringen. Die offene Synovektomie sollte nicht bei weitgehend zerst?rtem Gelenk mit signifikantem Knorpel-Knochen-Verlust der Gelenkoberfl?chen durchgeführt werden. überarbeitete Fassung aus: Orthop. Traumatol. 2 (1993), 244–250 (englische Ausgabe).     

Conus medullaris injury following both tetracaine and lidocaine spinal anesthesia

Multiple reports of cauda equina syndrome and transient radicular nerve root irritation have suggested that lidocaine spinal anesthesia may be responsible. In this case report, a patient with a preexisting diabetic neuropathy received a partial block following a tetracaine spinal, which was followed by a lidocaine spinal. Following block resolution, a new conus medullaris syndrome was diagnosed. Because of the close proximity of the cauda equina and the conus medullaris, differentiation between these syndromes can be difficult. The preexisting diabetic neuropathy may have predisposed this patient to neurologic injury. The choice of a different local anesthetic drug with less neurotoxic potential such as bupivacaine may have prevented this injury.     

Multiply Recurrent Trichilemmal Carcinoma With Perineural Invasion and Cytokeratin 17 Positivity

BACKGROUND: Trichilemmal carcinoma is an uncommon cutaneous malignancy that is thought to be the malignant counterpart of the trichilemmoma. Despite histologic features such as pronounced cytologic atypia, trichilemmal carcinoma is often described as having a rather benign clinical course. Cases of tumor recurrence after therapy are uncommon, and tumor neurotropism has never been described. OBJECTIVE: A case of multiply recurrent trichilemmal carcinoma with perineural invasion is described. The outer root sheath differentiation of this neoplasm is confirmed with the use of novel antibodies directed toward cytokeratins that are expressed in this area of the hair follicle. METHODS: The trichilemmal carcinoma was excised using the Mohs surgical technique. Tissue obtained during the extirpation of the tumor was subjected to immunohistochemical staining for cytokeratin 15, cytokeratin 17, and c-erb-B2. RESULTS: Tumor neurotropism was noted. The trichilemmal carcinoma demonstrated abundant cytoplasmic staining for cytokeratin 17 and c-erb-B2. CONCLUSIONS: In distinction to previous reports, this case reveals that trichilemmal carcinoma can demonstrate significant biological aggression, as reflected by tumor neurotropism and by failure to respond to multiple surgical excisions. The purported outer root sheath differentiation of this neoplasm is confirmed with the use of novel immunohistochemical staining. This immunohistochemical staining may be useful in differentiating trichilemmal carcinoma from other clear cell neoplasms.     

Medical Necessity in Canadian Health Policy: Four Meanings and . . . a Funeral?

Four meanings of medical necessity have emerged, evolved, and dominated past and current health policy debates about the appropriate level of service coverage under Canada's health insurance program. To explore the shift in definition, provincial government and national health care association position papers responding to federal legislative and policy reviews of Canada's health insurance program from 1957 to 1984 were examined, as were more current reports on medical necessity. Four meanings of medical necessity predominated: "what doctors and hospitals do"; "the maximum we can afford"; "what is scientifically justified"; and "what is consistently funded across all provinces." These meanings changed with time as different stakeholder associations and governments redefined the concept of medical necessity to achieve different policy objectives for health service coverage under Canada's health insurance program.     

Therapy of refractory/relapsed acute myeloid leukemia and blast crisis of chronic myeloid leukemia with the combination of cytosine arabinoside,tetrahydrouridine, and carboplatin

Summary Eight patients, of whom four had acute myeloid leukemia (AML) and four had chronic myeloid leukemia (CML) blast crisis, were treated with a combination of cytosine arabinoside (ARA-C: 1,600 mg/m² in three patients, 1,200 mg/m² in five patients), tetrahydrouridine (THU: 2,800 mg/m² in two patients, 2,646 mg/m² in one patient, 2,100 mg/m² in five patients), and carboplatin (900 mg/m² in four patients, 720 mg/m² in one patient, 450 mg/m² in three patients). As a result of this treatment, five of the eight patients became aplastic. Two of the four patients with CML blast crisis reverted to the chronic phase and two of the four patients with acute nonlymphocytic leukemia (ANLL) attained a remission (one partial remission and one complete remission). The major toxicities included myelosuppression, unacceptable hepatotoxicity, and diarrhea. Pharmacokinetics studies revealed that the addition of carboplatin did not significantly change the disposition of ARA-C. ARA-C levels were not significantly changed in comparison with those obtained in a prior study of ARA-C with THU (ARA-C plasma levels at 3 h, 2630±1170 ng/ml).Supported by the Don Monti Memorial Research Foundation