MRI findings in Hirayama’s disease: flexion-induced cervical myelopathy or intrinsic motor neuron disease?

Hirayama’s disease is a benign juvenile form of focal amyotrophy affecting the upper limbs. Previous studies have suggested that the disorder is a neck flexion induced cervical myelopathy. We report clinical and magnetic resonance imaging findings in nine patients with Hirayama’s disease. Cervical imaging of seven patients revealed spinal cord changes consisting of focal atrophy and foci of signal alterations. On neck flexion a forward movement and mild reduction in the anteroposterior diameter of the lower cervical cord against the vertebral bodies was noted in affected individuals as well as in five normal controls. In contrast to earlier reports, none of our patients showed complete obliteration of the posterior subarachnoid space. Measurement of the anteroposterior spinal cord diameter in each vertebral segment (C4–C7) revealed no significant differences in the degree of spinal cord flattening between the two groups. Furthermore, two of our patients had significant degenerative changes in the cervical spine (disc herniation, retrospondylosis) contralateral to the clinically affected side. These degenerative changes resulted in a marked cord compression on neck flexion but were not associated with ipsilateral clinical abnormalities or spinal cord alterations. Our results argue against a flexion-induced cervical myelopathy and support the view that Hirayama’s disease is an intrinsic motor neuron disease. Received: 15 March 1999 Received in revised form: 25 May 1999 Accepted: 1 June 1999     

Deep sclerectomy ab externo with implant: description of surgery technique

The authors present the modified associated technique of deep sclerectomy ab externo with implant. The indications, advantages and disadvantages are presented.     

Selective decontamination of the digestive tract helps prevent bacterial infections in the early postoperative period after liver transplant

In liver transplant (LTx) recipients, gut-associated bacterial and fungal organisms produce significant postoperative morbidity and mortality. We sought to assess the role of selective digestive decontamination (SDD) in preventing postoperative infections in a large single-center cohort of liver recipients transplanted under two non-simultaneous protocols. In 212 consecutive patients transplanted between 1/1/91 and 7/31/92, SDD (gentamicin 80 mg, polymyxin B 100 mg, nystatin suspension 10 mL) was employed, starting after induction of anesthesia and continued until POD 21 (SDD Group). In 157 consecutive patients transplanted between 1/1/93 and 12/31/93, SDD was not used (non-SDD Group). Both groups received IV vancomycin and cefotaxime prophylaxis. All culture-positive infections within the first 30 days post-LTx were recorded and classified as bacterial or fungal. Infection-related mortality (patients who died of infectious complications without any technical complication) was recorded. Groups did not differ in patient demographics, United Network for Organ Sharing (UNOS) status, use of veno-venous bypass, total/warm ischemia, or length of ICU stay. Infections developed in fewer SDD patients (56/212; 26%) than non-SDD patients (69/157; 44%) (p<0.001). The incidence of gram-negative infection was less in the SDD group (11% vs. 26%, p<0. 001) as was gram-positive infection (16% vs. 26%, p<0.001). Among patients who developed infection, there was no difference between groups in infections per patient. Primary graft non-function (PNF) developed in 20 SDD patients (7/20 had infections) and 8 non-SDD patients (6/8 had infections) (p=0.06). There were no differences in incidence of fungal infections or of infection-related mortality between groups. In the SDD group, there were fewer abdominal (p<0. 001), lung (p<0.001), wound (p<0.01), and urinary tract infections (p<0.05). CONCLUSION: Use of SDD in liver recipients early after transplant was associated with significantly fewer infections in the early postoperative period.     

Natural killer sensitivity of tumor cells isolated from primary and metastatic lesions of four Bomirski melanoma variants

Natural killer (NK) sensitivity of melanoma cells isolated from primary and metastatic lesions of four Bomirski melanoma variants was compared. The hamster melanomas differed in their growth rate and metastatic pattern. We found that during tumor growth of all the variants tested, NK sensitivity of melanoma cells at the metastasis formation stage was significantly lower in both primary and metastatic tumors than in cells isolated from primary tumors at transplantation. In the case of Ma, Ab and Ab-455, NK sensitivity of primary tumor cells was higher than that of the cells isolated from metastatic deposits. These data obtained from a spontaneous metastasis tumor model argue for the role of NK cells in preventing metastatic spread of Bormirski melanomas studied.     

Adrenergic stimulation of isolated rat gastric mucosal cells

Summary Adrenergic stimulation of the adenylate cyclase (AC)-cAMP-system and ¹⁴C-aminopyrine accumulation, an indirect measure of parietal cell H⁺-production, was studied in different preparations of gastric mucosal cells.The ₂-adrenoceptor agonist hexoprenaline activated AC of crude homogenates from the gastric corpus of mouse, rat, guinea-pig, hog, dog and man. In isolated rat gastric cells (20% parietal cells), treated by low power sonication, 10^–8 to 10^–3 mol/l adrenaline and hexoprenaline activated AC equally potently and efficaciously by maximally 170%. Isoprenaline proved to be less effective activating up to 80%. 5·10^–5 mol/l GMP-PNP augmented basal activity 8.5 times and reduced the maximal efficacy. Adrenaline and hexoprenaline activated AC by maximally 120%, isoprenaline by 40%. The potency of adrenaline was 4 times lower, that of hexoprenaline 2 and that of isoprenaline 4 times higher in the presence of GMP-PNP. Adrenergic stimulation was inhibited by the -adrenoceptor antagonist propranolol, the effect of -adrenoceptor-blockade by phenoxybenzamine was less pronounced. In fractions with 7–80% of parietal cells, prepared by isopycnic centrifugation with Percoll, adrenaline and hexoprenaline activated AC or hexoprenaline enhanced the cellular level of cAMP in parietal cell poor and rich fractions. The degree of activation in response to histamine correlated with the number of parietal cells. ¹⁴C-Aminopyrine uptake was increasingly stimulated through 10^–8 to 10^–5 mol/l hexoprenaline, maximally by doubling the basal accumulation. 10^–4 mol/l histamine was 8 times more effective. 3·10^–7 mol/l propranolol inhibited the effect of 10^–5 mol/l hexoprenaline by 80%.The data suggest the localization of -adrenoceptors (likely -adrenoceptor) on parietal and other nonidentified gastric cells. At the parietal cell, adrenaline and hexoprenaline initiate activation of AC and hexoprenaline leads to H⁺-production. The responses are small compared to the effect of histamine. Thus, -adrenoceptor agonists exert intrinsic activity in relation to H⁺-production. Their influence on stimulated secretion of isolated cells remains to be elucidated.     

Effect of therapeutic drug monitoring of amitriptyline and genotyping on efficacy and safety of depression therapy

Modern pharmacotherapy is based on precise adjustment of a dosage schedule to individual requirements of patient. Therapeutic drug monitoring is a method that allows for a more effective treatment approach, especially in the case of a narrow therapeutic index of a drug. Tricyclic antidepressant drugs are characterised by narrow therapeutic index as well as relationship between serum drug concentration and side effects. It was demonstrated that interindividual variability of blood concentrations of tricyclic antidepressant drugs is related to genetic polymorphism of oxidating enzymes participating in metabolism of these drugs. The aim of the study was to estimate the impact of therapeutic drug monitoring of tricyclic antidepressant drugs as well as genotyping on efficacy and safety of endogenous depression therapy. The study included 9 patients with established diagnosis of endogenous depression. Blood serum concentrations of amitryptyline was measured by fluorescence polarisation immune assay (FPIA, Abbott system). Genotype of cytochrome P450 isoenzyme CYP2D6 was determined using PCR-RFLP method. It was demonstrated that monitoring therapy of tricyclic antidepressant drugs in combination with determination of the genotype seems to be more safe and effective. Monitoring therapy and genotyping may be less expensive than the costs of prolonged hospitalisation and risk of side effects.     

Expression of extracellular matrix metalloproteases inducer on micrometastatic and primary mammary carcinoma cells.

PURPOSE: EMMPRIN (extracellular matrix metalloprotease inducer) is a glycosylated member of the immunoglobulin superfamily known to stimulate the production of matrix metalloproteases (MMPs) 1, 2, and 3 and MT1-MMP in peritumoral fibroblasts. We here evaluated whether EMMPRIN expression is related to tumor progression in human breast cancer. EXPERIMENTAL DESIGN: An immunohistochemical study using high-density tissue microarrays (n = 2222 breast cancer samples) and EMMPRIN-specific antibodies HIM6 and MEM-M6/1 was performed, and staining results were statistically correlated with various clinicopathological parameters. To analyze the putative association between EMMPRIN expression and bone marrow (BM) micrometastasis, an additional set of 55 breast tumors from patients with or without micrometastatic cells as determined with anti-cytokeratin antibody A45-B/B3 were included in our study. Cytokeratin-positive cells in BM were costained with EMMPRIN-specific antibody 1G6.2. RESULTS: Positive EMMPRIN staining correlated significantly with various histopathological risk factors (higher tumor grade, increased tumor size, negative estrogen receptor status and progesterone receptor status, and higher mitotic index) as well as decreased tumor-specific survival (log-rank, P = 0.0027). In particular, in patients > 50 years (i.e., postmenopausal women), EMMPRIN expression was an independent prognosticator as shown by Cox regression analysis (relative risk = 1.7, 95% confidence interval 1.4-4.3, P = 0.036). An involvement of EMMPRIN in tumor progression was also supported by the fact that it was expressed on approximately 90% of micrometastatic cells in BM. CONCLUSIONS: EMMPRIN expression in primary tumor predicts an unfavorable prognosis in breast cancer, suggesting a crucial role of EMMPRIN in progression of human mammary carcinomas.     

Elevated expression of carcinoembryonic antigen-related cell adhesion molecule 1 promotes progression of non-small cell lung cancer.

PURPOSE: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) has recently been implicated in cancer development and progression. This study was performed to assess whether CEACAM-1 expression in primary tumors is correlated to long-term survival in patients with operable non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Primary tumors of 145 consecutive patients with completely resected NSCLC (pT(1-4) pN(0-2) M(0) R(0)) were stained immunohistochemically using the monoclonal anti-CEACAM-1 antibody 4D1/C2. The prognostic relevance of CEACAM-1 expression was evaluated by univariate Kaplan-Meier and multivariate Cox regression analysis. The median follow-up period was 72 months (range, 10-130 months). RESULTS: Normal bronchiolar epithelium present in all sections exhibited no immunostaining. In contrast, 73 tumors (50.4%) showed between 1 and 66% CEACAM-1 positive tumor cells, and 72 tumors (49.6%) exhibited even a higher percentage of positive tumor cells. A high CEACAM-1 expression rate (i.e., >/=66% positive tumor cells) was more frequent in adenocarcinomas than in squamous cell carcinomas (61.9 versus 35.7%, respectively). Multivariate Cox regression analysis demonstrated that CEACAM-1 represents an independent prognosticator for cancer-related survival (P = 0.018; relative risk, 1.8; 95% confidence interval, 1.1-2.8). Subgroup analysis revealed that a high CEACAM-1 expression rate was of significant prognostic impact in pN(1)-pN(2) patients (n = 60; P = 0.024), pT(3)-pT(4) patients (n = 22; P = 0.009), and stage IIa-IIIa patients (n = 69; P = 0.012). CONCLUSIONS: The absence of CEACAM-1 in normal lung tissue and its expression in tumor cells argues against a tumor-suppressive role of CEACAM-1 in NSCLC. The correlation between elevated CEACAM-1 expression and an unfavorable prognosis indicates rather that CEACAM-1 might promote lung cancer progression.