Thrombotic thrombocytopenic purpura in 13 Dutch centres: treatment and longterm follow-up

OBJECTIVE: Analysis of the incidence, treatment modalities and disease course of thrombotic thrombocytopenic purpura (TTP) in the Netherlands. DESIGN: Retrospective follow-up study. SETTING: 13 centres in the Netherlands. METHODS: Regarding all patients admitted between 1-1-1979 and 1-1-1992 to one of 13 Dutch haematological centres, in whom the diagnosis of TTP was made for the first time, information was gathered from the medical records and from the patients own physicians on patient characteristics at presentation and the occurrence of relapse or death. The follow-up period tended on 1-4-1995. RESULTS: A total of 65 patients with newly diagnosed TTP were identified: 0.34 per 1,000,000 persons a year (95% confidence interval (95%-CI): 0.26-0.45), increasing to 0.83 in the last year of the study. Forty-six (95%) patients were treated with fresh frozen plasma: 18 (28%) by plasma infusion and 44 (68%) by plasma exchange; 48 (74%) (additionally) received corticosteroids. All 52 patients (80%) who survived the first four weeks after admission reached complete remission. Twelve patients with relapsing TTP underwent splenectomy in remission. The 5-year survival rate was 77% (95% CI: 66-87) and the 5-year relapse-free survival rate 38% (95% CI: 25-52). Cardiac symptoms, severe thrombocytopenia and a high serum LDH were risk factors for acute mortality, but no risk factors for relapse or late-occurring death could be identified. CONCLUSION: TTP is a rare disease which is increasingly being recognized. Plasma exchange and corticosteroids are the most frequently used therapies. The disease has a high mortality rate in the acute phase of the disease.     

Corneal blood staining following autologous blood injection for hypotony maculopathy

We experienced the case of left atrial myxoma originating from posterior leaflet mitral valve. Mitral valve repair was performed in that case, because of the presence mitral leaflet defect due to removal of the myxoma. Transesophageal echocardiography was a useful tool for perioperative evaluation of the mitral valve and precise localization of the origin of the myxoma.     

Enhanced endothelin-mediated coronary vasoconstriction and attenuated basal nitric oxide activity in experimental hypercholesterolemia

Matrix metalloproteinases (MPs) constitute a family of proteolytic enzymes (proteases) that degrade extracellular matrix (ECM) and promote the local or metastatic potential of carcinoma cells, and whose action is restrained by special inhibitors (metalloproteinase inhibitors; MIs). We assessed the role of the MPs stromelysin-3 (STR-3), putative metalloproteinase-1 (PUMP-I), and the gelatinases of molecular weights 72 kDa and 92 kDa, as well as the role of their inhibitors tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2, as markers of metastatic potential in 25 fresh biopsies of squamous-cell lung carcinomas (SCLCs). We examined levels of messenger ribonucleic acid (mRNA) expression for these MPs and inhibitors through Northern blot analysis in 10 carcinomas of high-to-moderate differentiation without lymph-node involvement, and in 15 infiltrative carcinomas of moderate-to-low differentiation with lymph-node involvement. Five cases with significant epithelial atypia and five samples with normal mucosa were used as controls. Expression of STR-3 and TIMP-2 was also assessed immunohistochemically with the avidin-biotin-complex (ABC) technique. We noticed a progressive increase in the expression levels of MPs, especially of STR-3, and of TIMP-2, from the stage of epithelial atypia to the detection of carcinoma, finding the highest values of these substances among carcinomas of low differentiation with nodal metastases. These findings were also confirmed with immunohistochemical analysis. Our results suggest that there is a significant association of the expression of MPs and MIs with both the local and metastatic potential and the degree of cellular differentiation of SCLC, and that this association is clinically important because of its prognostic and therapeutic implications.     

Functional connectivity in the rodent trigeminal pathway grown in vitro

In explant cocultures of the rat trigeminal pathway, embryonic trigeminal ganglion cells grow their axons into peripheral cutaneous and central nervous system targets (R.S. Erzurumlu, S. Jhaveri, Target influences on the morphology of trigeminal axons, Exp. Neurol, 135 (1995) 1-16; R.S. Erzurumlu, S. Jhaveri, H. Takahashi, R.D.G. McKay, Target-derived influences on axon growth modes in explant cocultures of trigeminal neurons, Proc. Natl. Acad. Sci. USA 90 (1993) 7235-7239). In heterochronic cocultures, composed of embryonic trigeminal ganglion, embryonic whisker pad and postnatal brainstem slice, trigeminal axons develop arbors and terminal boutons in the brainstem trigeminal nuclei. To determine whether these terminal arbors establish functional connections with the brainstem neurons, we examined the electrophysiological properties of brainstem neurons and their responsiveness to trigeminal ganglion stimulation. Intracellular recordings were done in vitro on cells of the trigeminal subnucleus interpolaris (SPI) in trigeminal pathway cocultures (E15 whisker pad, E15 trigeminal ganglion, and postnatal day (PND) 0-2 brainstem slice) or in the SPI of acutely prepared brainstem slices. Electrophysiological properties of SPI cells in both preparations were virtually identical. The voltage responses of SPI neurons to intracellular current injection were highly linear suggesting they lacked a number of voltage-dependent conductances. Depolarizing current injection produced trains of action potentials with a frequency that varied with stimulus intensity. In explant cocultures, electrical activation of the trigeminal ganglion evoked EPSPs, and EPSPs coupled with IPSPs in SPI cells. Bicuculline blockade of IPSP activity resulted in long lasting EPSPs whose duration increased with membrane depolarization. These results show that brainstem trigeminal neurons can retain their functional properties in culture and establish functional connections with primary sensory afferents.     

Antisense-mediated resistance to measles virus infection in HeLa cells

Endogenous expression of antisense RNA in transfected cells has been explored for use in blocking cellular gene expression and for its antiviral potential. Antisense strategies were used with the goal of blocking measles virus (MV) infection. A recombinant expression plasmid was designed to produce antisense oligonucleotides targeted to the 5' end of the MV nucleocapsid protein mRNA. This construct was transfected into HeLa cells. The transfected cell line and a control cell line expressing a random RNA comprising the same nucleotides were infected with MV and assessed for viral resistance by observation of cytopathic effect (CPE); infectious virus was quantified by viral plaque assay. Both cell lines were also infected with a related paramyxovirus, mumps virus, as a specificity control. Both CPE and infectious virus were reduced by approximately 90% in the antisense-expressing line compared with that in control cells or transfectant cells expressing random RNA. There was no evidence of resistance to infection with mumps virus in any cell line.     

Identification of nursing management diagnoses

Theories from nursing and management provide frameworks for enhancing effectiveness of nursing management practice. The concept nursing management diagnosis has been developed by integrating nursing diagnosis and organizational diagnosis as a basis for nurse manager decision-making. Method triangulation was used to identify problems of managing nursing units, to validate those problems for relevancy to practice, to generate nursing management diagnoses, and to validate the diagnoses. Diagnoses were validated according to a definition of nursing management diagnosis provided. Of the 72 nursing management diagnoses identified, 66 were validated at a 70% level of agreement by nurse managers participating in the study.     

Colectomy for sigmoid volvulus

PURPOSE: Volvulus of the sigmoid carries a high mortality. This minimally invasive technique is designed for poor-risk patients. TECHNIQUE: Aided by laparoscopy, the mobile sigmoid is exteriorized through a mini-incision without preliminary dissection. The entire resection and anastomosis is performed on the surface of the abdomen. The options of end colostomy, primary anastomosis with or without fecal diversion, can all be used with this method. RESULTS: No mortality or leakage occurred in four patients. CONCLUSION: This rapid operation does not require advanced laparoscopic skills. Preliminary results should be confirmed by others.     

Association of fragile X syndrome with delayed replication of the FMR1 gene

The fragile X syndrome is commonly associated with mutant alleles of the FMR1 gene that are hypermethylated and have large expansions of CGG repeats. We present data here on the replication timing of FMR1 that confirm predictions of delayed replication of alleles from affected males. The normal FMR1 allele replicates late in S phase, while alleles from affected males replicate later, the major peak of replication occurring in the flow cytometry fraction usually referred to as G2/M. The delayed timing of replication is not the direct result of a single replication fork stalling at the expanded CGG repeat, because delayed replication was observed for regions on both sides of the repeat. The domain of altered replication timing includes sites at least 150 kb 5' and 34 kb 3' of the repeat, indicating that genes in addition to FMR1 may be affected.     

Conventional consent with opting in versus simplified consent with opting out: an exploratory trial for studies that do not increase patient risk

PURPOSE: This study aimed to analyze the results of laser in situ keratomileusis (LASIK) in different degrees of myopia. MATERIAL AND METHODS: Three hundred consecutive eyes were divided into 4 groups according to their degree of preoperative myopia. Group I was between -3 and -6 diopters (D) (28 eyes), low myopia. Group II was between -6.25 and -10 D (138 eyes), moderate myopia. Group III was between -10.25 and -15 D (91 eyes), high myopia. Group IV was between -15.25 and -25.50 D (43 eyes), extremely high myopia. Patients were observed for 6 to 25 months. RESULTS: For group I, the preoperative spherical equivalent was -5.12 D +/- 0.81 standard deviation (SD), corrected visual acuity was 0.88 +/- 0.14 (SD), and keratometry was 44.09 D +/- 1.65 (SD). At the last check-up, the spherical equivalent was -0.42 D +/- 0.98 (SD), corrected visual acuity was 0.89 +/- 0.15 (SD), keratometry was 39.11 D +/- 1.61 (SD). For group II, preoperative spherical equivalent was -8.33 D +/- 1.24 (SD), corrected visual acuity was 0.72 +/- 0.22 (SD), keratometry was 44.34 D +/- 1.64 (SD). At last check-up, the spherical equivalent was -0.19 D +/- 1.22 (SD), corrected visual acuity was 0.76 +/- 0.17 (SD), keratometry was 37.56 D +/- 1.90 (SD). For group III, the preoperative spherical equivalent was -12.37 D +/- 1.49 (SD), corrected visual acuity was 0.58 +/- 0.23 (SD), and keratometry was 44.06 D +/- 1.63 (SD). At last check-up, spherical equivalent was -0.55 D +/- 1.63 (SD), corrected visual acuity was 0.61 +/- 0.18 (SD), and keratometry was 35.88 D +/- 2.18 (SD). For group IV, the preoperative spherical equivalent was -19.04 +/- 2.82 (SD), corrected visual acuity was 0.37 +/- 0.17 (SD), and keratometry was 44.02 D +/- 1.30 (SD). At last check-up, spherical equivalent was -1.49 D +/- 1.54 (SD), corrected visual acuity was 0.44 +/- 0.18 (SD), and keratometry was 33.94 D +/- 2.54 (SD). CONCLUSION: With some exceptions, LASIK results generally are acceptable and stable. Nevertheless, the scatter of some cases shows that there is room for improvement, even in the most sophisticated excimer software. The high regression of group I proves the need to sample multizone software to determine whether stability is improved. Although visual results are better in patients with lower myopia, the patients whose eyes had higher ametropia more often showed improvement in their visual acuity. This may be because of the greater postoperative size of the image on the macula.