Cisplatin neuropathy: clinical course and neurophysiological findings.

Sixteen patients treated with cisplatin (CDDP) 40 mg/m2 on days 1-5 every 4 weeks for three courses (cumulative dose 600 mg/m2) were clinically and neurophysiologically tested before, during and 1, 3, 6, 9 and 12 months after CDDP administration. The first symptoms of polyneuropathy occurred in 4 of 9 patients after the second course (cumulative dose 400 mg/m2). One month after treatment 1 of 9 patients was asymptomatic, 5 complained of symptoms and 3 showed clinical and neurophysiological signs of polyneuropathy. Three months after CDDP all patients were affected. Clinical and neurophysiological signs of severity progression were noted up to 6 months after treatment with CDDP.

SFEMG in ocular myasthenia gravis diagnosis.

BACKGROUND AND OBJECTIVE: In typical cases, the patient's history and clinical examination make it possible to diagnose ocular myasthenia gravis (OMG). But, in many cases a clear clinical picture is not present and OMG diagnosis is very difficult because gold diagnostic standard tests are not available. The diagnostic tests for OMG are usually unable to display a good sensitivity and specificity simultaneously. In this paper, we studied 86 cases submitted for suspected OMG. METHODS: The patients were studied clinically and with various other tests used in OMG diagnosis (SFEMG, repetitive nerve stimulation, Ab anti AChR titration, tensilon test). RESULTS AND CONCLUSION: SFEMG showed the highest sensitivity (100%) while Ab anti AChR showed the highest specificity (100%). To our knowledge this is the largest population of suspected OMG studied using most of the diagnostic parameters, reported in the literature.

Molecular analysis of Drosophila melanogaster AdhnLA405 confirms reliability of DNA-sequencing methodology.

An alcohol dehydrogenase (ADH) null mutant of Drosophila melanogaster (AdhnLA405) originally recovered following X-ray irradiation of mature sperm (Aaron, 979) is analyzed by Southern blotting, Western blotting, and DNA sequencing. The genetic, immunologic, and nucleic acid sequence data are consistent with the hypothesis that a cross-over event, independent of X-irradiation, between parental chromosomes is responsible for the ADH null phenotype of AdhnLA405. By DNA-sequence analysis we show that molecular cloning of this locus (i.e., propagation in prokaryotic hosts) apparently does not introduce any spurious changes (substitutions, additions, deletions, or rearrangements) within the DNA.

Efficacy and toxicity of very high-dose cisplatin in advanced ovarian carcinoma: 4-year survival analysis and neurological follow-up.

Given the steep dose-response relationship with cisplatin, a pilot study on very high-dose cisplatin (HD-CDDP) was conducted in previously untreated patients with advanced ovarian carcinoma and postoperative residual tumor (RT). Thirty-seven patients (FIGO stages III-IV; RT> 0.5 cm) received three courses of HD-CDDP (a course of 40 mg m-2 day-1 for days 1-5, every 28 days). Twenty patients (54%) achieved clinical complete response (CR), 12 (32%) partial response (PR), and the remaining five (14%) showed stable or progressive disease (NC-P). All 20 clinically complete responders underwent second-look laparotomy and CR was confirmed in all but five cases (pathologic CR: 40%) and in 71% of patients with> 0.5-2 cm RT vs. 15% of those with> 2 cm RT (P < 0.001). The 4-year overall survival was 35% (median: 27 months, range: 7-58+), and 53% vs. 20% for patients with> 0.5-2 cm and> 2 cm RT, respectively (P = 0.01). The overall progression-free survival was 29.5% (median: 16 months, range 2-58+) and for patients with more or less than 2 cm RT it was 20 and 41.2% (P < 0.05). Pathologically complete responders received no further treatment and showed a 3-year disease-free survival of 53%. The major toxic effect was a delayed-onset peripheral neuropathy observed in all patients, five of them (13.5%) with gait disturbances requiring continuous assistance. Nevertheless, none of them became wheelchair dependent and about 90% of the alive patients recovered at the 18-month neurologic follow-up, suggesting that cisplatin damage can be reversible. Ototoxicity was detected in all patients although only 19% of patients were symptomatic. HD-CDDP showed high activity in patients with> 0.5-2 cm RT, suggesting that the adverse significance of minimal RT may be partially overcome through an intensive chemical cytoreduction. Substantial neurotoxicity and the need for intensive care represent the major drawbacks. Further studies should delineate the exact role of HD-CDDP in optimally debulked patients, and a considerable effort should be made in rapidly achieving reliable data on the value of neuroprotectors in the prevention of the dose-limiting neurotoxicity.

Retinal vascular endothelial growth factor (VEGF) mRNA expression is altered in relation to neovascularization in oxygen induced retinopathy.

The temporal and spatial expression of vascular endothelial cell growth factor (VEGF) mRNA was studied in normal developing cat retina, and in oxygen induced retinopathy. Unexposed control and oxygen-exposed animals (80 h of 80% oxygen from day 3, n = 16) were studied at 1, 2, 4, and 6 weeks after birth. India ink injected retinal flat mounts were used to study vessel progression, and in situ hybridizations using retinal cross sections were used to assess VEGF mRNA accumulation. In controls, as the retina matured, VEGF mRNA hybridization was evident in the ganglion cell layer in a scattered line of distinct cells prior to the ingrowth of vessels, involved the most cells in regions just peripheral to invading vessels and persisted in a fewer positive cells, widely spaced in the vascularized retinas of control, six week animals. In the inner nuclear layer, hybridization initially appeared diffusely and later became localized to a narrow portion of that layer and persisted there. In animals with oxygen induced retinopathy, a substantial increase in hybridization was observed in both the ganglion cell and inner nuclear layers of the avascular retina anterior to the advancing neovascularization. VEGF hybridization decreased abruptly to background levels in both layers at the point were neovascularization met avascular retina. By six weeks, when the neovascularization reached the ora, there was a return of VEGF mRNA in the inner nuclear layer which was similar to normal control expression. A low level of unchanging expression was also observed in the retinal pigment epithelium in both groups at all ages. These results indicate that VEGF mRNA abundance is regulated during retinal vascularization and is increased in relation to oxygen induced neovascularization, suggesting that VEGF may play an important role in both normal retinal vessel development and in the pathophysiology of retinopathy of prematurity.

Lambert-Eaton myasthenic syndrome: a clinical contribution.

A case of Lambert-Eaton myasthenic syndrome (LEMS) revealed by prolonged apnea following the administration of pancuronium during surgery for squamous cell carcinoma of the lung is reported. The postoperative respiratory failure allowed the correct interpretation of a poor clinical picture:slight weakness of the lower limbs and no other signs of neuromuscular disease. In the authors' opinion prolonged apnea always requires accurate neurophysiological investigation in order to detect latent neuromuscular transmission defects which are frequently underevaluated.

Search for the genome of bovine herpesvirus types 1, 4 and 5 in bovine semen.

Bovine herpesvirus type 1 (BoHV-1) causes respiratory and reproductive disorders in cattle. Recently, bovine herpesvirus type 5 (BoHV-5) and bovine herpesvirus type 4 (BoHV-4) have been identified to be associated with genital disease. In this study, the presence of the genome of BoHV-1, BoHV-4 and BoHV-5 in bovine semen of Argentinean and international origin was analyzed by PCR assays. The most important finding of this study is the detection of the genome of BoHV-1 and BoHV-4 in semen of bulls maintained at artificial insemination centers. It is particularly relevant that BoHV-1 DNA was also identified in one sample of international origin suggesting the need for extensive quality control measures on international transport of bovine semen.

Detection of bovine leukemia virus specific antibodies using recombinant p24-ELISA.

We developed an indirect ELISA test (rp24-ELISA) for the detection of antibodies against the p24 capsid protein of bovine leukemia virus (BLV) in bovine serum samples. A recombinant p24 (rp24) was expressed in the Escherichia coli expression system, purified in a nickel charged resin and used as antigen in the ELISA test. A cut-off point was established considering the distribution of reactivity values obtained by rp24-ELISA on a set of 555 field serum samples that were stated as double positive (DP) or double negative (DN) by the combination of commercial agar gel immunodiffusion (AGID) assay and gp51-ELISA tests results. The rp24-ELISA showed good concordance with the agar gel immunodiffusion assay, when 710 serum samples were analyzed. In addition, rp24-ELISA demonstrated to be a precise assay with good repeatability and reproducibility and a better analytical sensitivity than AGID. From 67 discordant rp24-ELISA-AGID sera, 4 negative reactors were from the DP group, 28 positive samples were from the DN group and 35 positive samples were stated as negative by AGID but positive by the gp51-ELISA. Samples from this last subgroup were sent to an OIE reference laboratory where 28 samples were stated as negative, 5 samples were stated as positive and 2 as inconclusive. Complete concordance with blind previous results from an international proficiency test panel confirmed the capability of the assay to discriminate between infected and non-infected animals. In conclusion, the rp24-ELISA developed and standardized demonstrated to have good analytical characteristics to be considered for screening of BLV.

Differential cytokine mRNA expression by neonatal pulmonary cells.

The purpose of this study was to describe cytokine profiles of human neonatal pulmonary cells isolated by tracheal aspiration (TA) and by deep pulmonary lavage (DPL). We hypothesized that mRNA phenotyping, using the technique of reverse transcriptase polymerase chain reaction (RT-PCR), would reveal differences in cytokine expression patterns between cells from proximal and distal airway compartments. We reasoned that cells derived by DPL may reflect pathogenic pathways indicative for the development of bronchopulmonary dysplasia in the premature infant. Here we have described the detection of mRNA for IL-1 alpha, IL-1 beta, IL-6, IL-8, and tumor necrosis factor-alpha. Fourteen paired TA and DPL samples from six premature infants were collected at 1, 7, or 28 d of age. Two of 14 samples were negative for beta-actin (a ubiquitous mRNA) by RT-PCR and were excluded from further analysis. Each of the remaining 12 samples expressed IL-8. Furthermore, each cytokine could be expressed by TA or DPL cells. Cytokine mRNA phenotype profiles were found to differ between TA and DPL cells in four of five paired samples. Our results show that cells retrieved from these two pulmonary compartments are sources for these cytokines and suggest that RT-PCR of TA/DPL cells can be used to test hypothetical predictive markers for the development of bronchopulmonary dysplasia.

Radiculomedullary complications of cervical spinal manipulation.

Spinal manipulation is commonly used by some therapists for the treatment of cervical pain. Flexion-extension of the cervical spine produces sliding movements of one vertebra over the one below it, which leads to physiological reduction in the antero-posterior diameter of the spinal canal. Spinal manipulation provokes movements that exceed the physiological limits of these articulations and thereby lead to a more significant reduction of the canal diameter. In patients with pre-existing stenosis of the canal or those with vertebral instability, these movements may cause (or aggravate) myelopathy. For this reason, a thorough neurological examination and cervical spine films should be considered mandatory in patients being considered for spinal manipulation. This report describes four patients with cervical myelopathy and/or radiculopathy caused or aggravated by spinal manipulation. In one patient, magnetic resonance scans before and after chiropractic treatment strongly suggests that the disc prolapse syndrome experienced by the patient was provoked by the spinal manipulation.

Mononeuropathy of a distal branch of the femoral nerve in a body building champion.

A unique case of a body building champion with localised atrophy of the distal portion of the vastus lateralis muscle is reported; neurophysiological evaluation suggests a selective lesion of a distal branch of the vastus lateralis nerve (a motor branch of the femoral nerve). A necroscopic study in four cases was performed to better clarify the site and mechanism of nerve lesion. The data suggest that stretching and compression of the nerve has probably occurred during strenous exercise.

Cell-specific expression of fibronectin in adult and developing rabbit lung.

Fibronectin (FN), a glycoprotein component of the extracellular matrix, plays a role in tissue morphogenesis and tissue-specific differentiation through its effects on cell adhesion, cell shape, and cytoskeletal organization. Immunohistochemistry has been used to show that during lung development FN deposition changes, yet the cell-specific sites of pulmonary FN synthesis have not been determined. Because cellular FN synthesis is reflected by FN mRNA abundance, we performed in situ hybridizations to identify pulmonary tissue with the capacity to synthesize FN. Both in situ mRNA hybridization and immunohistochemical staining were performed on tissue sections from lungs of adults and late gestation fetal and neonatal rabbits. In adults, FN transcripts and immunostaining were clearly seen in endothelial cells, smooth muscle cells, and chondrocytes. During lung development, FN transcripts were virtually ubiquitous except in airway epithelium. There was a gradual decrease in FN mRNA abundance with advancing fetal age, but low levels of FN mRNA persisted in neonatal and adult lungs. In contrast, parenchymal immunostaining increased throughout fetal development and remained elevated in the newborn. FN immunostaining was lower in adult lung. In all tissues examined, airway epithelial cells contained no FN transcripts above background. However, immunostaining was detected in airway basement membrane zones and on luminal surfaces of some epithelial cells. The lack of FN transcripts in airway epithelial cells suggests that FN synthesis does not normally occur in this cell type and that its associated FN immunostaining is from another source. The colocalization of FN mRNA and protein in pulmonary endothelial cells, smooth muscle cells, and chondrocytes in adults strongly suggests that these cells are sites of FN synthesis.

Fibronectin expression in bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic fibrotic lung disease of neonates. Fibronectin (FN), a component of the extracellular matrix, is increased in the tracheobronchial effluent of neonates destined to develop BPD. Pulmonary FN is derived from plasma and local cellular synthesis. In order to identify which pulmonary cells synthesize FN and to test the hypothesis that FN is more abundant in lungs with BPD, we examined the distribution of pulmonary FN by in situ hybridization (for mRNA) and immunohistochemistry (for protein) in neonatal autopsy lung specimens, comparing lungs with BPD to those without. We used a staging system in which BPD is characterized by disruption of alveolar architecture, severe vascular changes, airway epithelial necrosis, smooth muscle hypertrophy, and peribronchial fibrosis. FN mRNA and protein were found in vascular endothelium, macrophages, fibroblasts, vascular and airway smooth muscle, and chondrocytes as well as in the pulmonary parenchyma in neonates with and without BPD. Hyaline membranes, when present, immunostained intensely for FN protein. FN mRNA was not seen in airway epithelial cells of either group. FN mRNA and protein were first increased in early acute BPD with their levels appearing greatest during the chronic reparative stage of BPD. In long-standing "healed" BPD, lower levels of FN mRNA and protein were seen. These findings are consistent with the association of increased FN with adult fibrotic lung disease and the previously reported increase in FN tracheal effluent levels in infants with BPD. Our results suggest an important role for pulmonary cell-derived FN in the early inflammatory and later proliferative stages of BPD.

Neurophysiological classification and sensitivity in 500 carpal tunnel syndrome hands.

OBJECTIVES: To evaluate the following points about carpal tunnel syndrome (CTS): 1) characterization of a wide population; 2) sensitivity of electrodiagnostic tests, and particularly the contribution of disto-proximal ratio test; 3) validity of a neurophysiological classification developed by us. MATERIAL AND METHODS: Prospective study in 500 hands with CTS symptoms. Neurophysiological "standard" tests were always performed: sensory nerve conduction velocity (SNCV) first- and third digit-wrist and distal motor latency (DML). In "standard negative" hands disto-proximal ratio technique (R) was performed. Neurophysiological classification: Extreme CTS (absence of median motor, sensory responses), Severe (absence of sensory response, abnormal DML), Moderate (abnormal SNCV, abnormal DML), Mild (abnormal SNCV, normal DML), Minimal (abnormal R or other segmental/comparative test, normal standard tests). RESULTS: Sensibility of standard tests: 77%. R increased the diagnostic yield by 20%. CTS classification appeared reliable with significant differences between groups. CONCLUSION: R is a useful test, the classification may be useful in clinical/therapeutical decisions.

Italian multicentre study of carpal tunnel syndrome: study design. Italian CTS Study Group.

In September 1996, during a carpal tunnel syndrome (CTS) symposium, the Italian CTS Study Group was funded. The group designed a strict clinical and neurophysiological protocol for performing a wide multicentre study on idiopathic CTS in hands. In addition to the traditional evaluations, the group also adopted a validated patient-oriented measurement in order to obtain comprehensive and reliable data for the clinical picture. The study was designed to: (1) better assess the clinical picture of the CTS population, especially using new measurement tools (patient-oriented); (2) evaluate the sensitivity of an electrodiagnostic protocol; (3) re-evaluate the validity of a neurophysiological classification; and (4) evaluate the influence of social status and quantify some of the aspects regarding economic and social costs. The study design is described.

A case of Guyon syndrome with neuroapraxic block resolved after surgical decompression.

Guyon syndrome is the well-known ulnar entrapment at the wrist; usually surgical decompression improves the symptoms. Neurophysiological studies are essential to demonstrate the abnormality of ulnar nerve conduction at the wrist. We report a case of Guyon syndrome onset after 6 h of cycling. Neurophysiological study revealed ulnar neuroapraxic block at the wrist, and axonal impairment. Post-operative clinical and neurophysiological follow-up showed marked clinical improvement and neurophysiological resolution of abnormalities. To our knowledge, no cases of Guyon syndrome with neuroapraxic block are reported in the literature.

Low-rate nerve stimulation during regional ischemia in the diagnosis of muscle glycogenosis.

Five patients with muscle glycogenoses (Gly), 30 normal subjects (NS), and 52 disease controls received 3 Hz repetitive stimulation of the ulnar nerve for 4 min (P-LRNS) during regional ischemia and during normal circulation. During regional ischemia, the compound muscle action potential (CMAP) of NS showed 8.5% (SE: 1.0) facilitation after 1 min of P-LRNS and 4.8 +/- 1.5% facilitation after 4 min. Gly showed 8.1 +/- 1.0% facilitation after 1 min of P-LRNS but -58.6 +/- 6.9% depression after 4 min of P-LRNS. During normal circulation, in 18 NS and 4 Gly tested, the facilitation detected after 1 min of P-LRNS was unchanged until the end of stimulation. Compared with the mean +/- 2 SD of NS, individual values of CMAP depression were abnormal in all Gly patients already by the 3rd min of ischemic P-LRNS. Of disease controls, myasthenia gravis patients only showed a CMAP depression during ischemic P-LRNS which was distinguishable from that detected in Gly, being mainly induced by neuromuscular transmission block.

Suprascapular nerve entrapment. Neurophysiological localization in 6 cases.

We report 6 cases of a suprascapular nerve lesion: 3 of them presented a nerve entrapment at the suprascapular notch and 3 at the spinoglenoid notch. Electrophysiological investigation localized the site of entrapment in all cases.

Interleukin-8 and monocyte chemoattractant protein-1 mRNAs in oxygen-injured rabbit lung.

The chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are neutrophil and monocyte attractants, respectively. We hypothesized that IL-8 and MCP-1 mRNA expression in alveolar macrophages (AM) lavaged from rabbit lung would be increased by oxygen exposure, which is known to induce inflammation. Adult rabbits were exposed to > 95% oxygen for up to 64 h and allowed to recover in room air for up to 72 h before killing and pulmonary lavage. Numbers of lavageable polymorphonuclear cells (PMN) and AM rose during the exposure protocol. Quantitative in situ hybridization with 3H-labeled cRNA probes showed both IL-8 and MCP-1 mRNA expression in AM during oxygen exposure, with peak levels of IL-8 mRNA at 56-h oxygen exposure and of MCP-1 mRNA at 64-h oxygen exposure with 24-h room air recovery. IL-8 mRNA was present in PMN between 48-h oxygen exposure and 64-h oxygen exposure with 24-h room air recovery. MCP-1 mRNA was not expressed in PMN. This pattern of chemokine mRNA expression emphasizes the importance of inflammatory cells as effectors in the pulmonary response to oxygen exposure.