A Decline in C6 Antibody Titer Occurs in Successfully Treated Patients with Culture-Confirmed Early Localized or Early Disseminated Lyme Borreliosis

C₆, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C₆-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C₆ antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C₆ negative or had a ≥4-fold decrease in C₆ antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C₆ negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C₆ antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis.     

A comparison of the sniff magnitude test and the University of Pennsylvania Smell Identification Test in children and nonnative English speakers

The sniff magnitude test (SMT) is a reliable and rapid clinical test of olfactory function that is minimally dependent on cognitive and linguistic abilities. In this study, we compared performance on the SMT and University of Pennsylvania Smell Identification Test (UPSIT) in samples of children and nonnative English speakers. Previous research has shown that these populations perform poorly on the UPSIT as compared with young, healthy U.S. adults. Such performance differences may reflect variations in memory/cognition and language/culture rather than olfactory abilities. The UPSIT scores of children and of Indian and Chinese graduate students were found to be lower than those of young U.S. adults. By contrast, these groups did not perform more poorly than U.S. adults did on the SMT. The results are consistent with findings from our studies, with the elderly showing that performance on the UPSIT, but not the SMT, is significantly correlated with measures of memory, language and other cognitive abilities. The findings highlight the utility of the SMT when evaluating the olfactory ability of the very young, older adults and people with diverse linguistic and cultural backgrounds.     

Tolerance of nonsteroidal anti-inflammatory drug-sensitive patients to the highly specific cyclooxygenase 2 inhibitors rofecoxib and valdecoxib.

BACKGROUND: Selective inhibitors of cyclooxygenase 2 (COX-2) are generally tolerated by patients sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-1. Valdecoxib is a new sulfonamide-containing COX-2-specific inhibitor indicated for the treatment of acute pain, osteoarthritis, and rheumatoid arthritis. OBJECTIVE: To compare the clinical tolerance to rofecoxib and valdecoxib in patients who previously developed urticaria and angioedema while taking classic NSAIDs. METHODS: Patients with challenge-proven NSAID cutaneous sensitivity were submitted to single-blinded controlled oral challenges with rofecoxib, 50 mg, and valdecoxib, 40 mg. RESULTS: Twenty-eight patients (19 females and 9 males; mean +/- SD age, 28.6 +/- 15.0 years; age range, 10-61 years) participated in this study. Twenty-two (85%) of 26 patients who underwent skin tests were atopic, as demonstrated by a clinical history of rhinitis and/or asthma plus positive immediate-type skin hypersensitivity test results. A previous exclusive cutaneous reaction pattern (urticaria and/or angioedema) had occurred in 10 patients (36%), whereas a mixed pattern of skin and respiratory symptoms had occurred in 18 patients (64%). Twenty patients (71%) were multiple reactors, and 8 patients (28%) were single reactors. In this current study, 2 patients (7%) taking rofecoxib experienced angioedema, and 1 patient (4%) taking valdecoxib experienced urticaria. CONCLUSIONS: Rofecoxib and valdecoxib can be safely used by most NSAID-sensitive patients with cutaneous reactions. Our findings suggest that isolated cross-reactions may occur in these patients, and for this reason, controlled oral provocation may be prudent when prescribing valdecoxib or rofecoxib for patients who have previously had urticaria or angioedema triggered by NSAIDs.     

Deletion spanning the 5′ ends of both the COL4A5 and COL4A6 genes in a patient with Alport's syndrome and leiomyomatosis

Alport's syndrome is characterized clinically by a nonimmune glomerulopathy, often accompanied by sensorineural hearing loss and lens abnormalities, frequently due to mutations in the COL4A5 gene. The association of AS with diffuse leiomyomatosis, a benign proliferation of smooth muscle that occurs most often in the esophagus, trachea, and female genitalia, has been reported. Recently, a deletion involving both the COL4A5 and COL4A6 genes has been reported in four unrelated families. We report an additional case with Alport's syndrome associated with leiomyomatosis carrying a deletion of both COL4A5 and COL4A6 genes. A detailed characterization of the genomic region involved in the deletion event has been performed. Our results demonstrate that the deletion removed exon l of COL4A5 and exons l and 2 of COL4A6. © 1994 Wiley-Liss, Inc.     

Vortex Shaped Current Sources in a Physical Torso Phantom

Recent studies reported differential information in human magnetocardiogram and in electrocardiogram. Vortex currents have been discussed as a possible source of this divergence. With the help of physical phantom experiments, we quantified the influence of active vortex currents on the strength of electric and magnetic signals, and we tested the ability of standard source localization algorithms to reconstruct vortex currents. The active vortex currents were modeled by a set of twelve single current dipoles arranged in a circle and mounted inside a phantom that resembles a human torso. Magnetic and electric data were recorded simultaneously while the dipoles were switched on stepwise one after the other. The magnetic signal strength increased continuously for an increasing number of dipoles switched on. The electric signal strength increased up to a semicircle and decreased thereafter. Source reconstruction with unconstrained focal source models performed well for a single dipole only (less than 3-mm localization error). Minimum norm source reconstruction yielded reasonable results only for a few of the dipole configurations. In conclusion active vortex currents might explain, at least in part, the difference between magnetically and electrically acquired data, but improved source models are required for their reconstruction.     

A B7-1-transfected human melanoma line stimulates proliferation and cytotoxicity of autologous and allogeneic lymphocytes

B7 co-stimulation is necessary to activate resting T cells upon antigen recognition by the T cell receptor. To see whether expression of B7 may render human melanoma cells able to stimulate T cells, a cloned melanoma line (Me1B6), which did not express B7-1, was transfected with the human B7-1 gene. In proliferation assays, B7-1 transfected cells (Me1B6/B7) showed greater stimulatory activity of allogeneic and autologous peripheral blood lymphocytes (PBL) compared to parental, non-transfected tumor cells. This effect was also seen when allogeneic CD8⁺ and CD4⁺ subpopulations were used as effectors. In these studies, activation of lymphocytes was B7-1-dependent and HLA classes I and II mediated. The higher proliferation correlated with an increased lytic activity by PBL stimulated with B7-1⁺ tumor cells against the untransfected Me1B6. Furthermore, PBL from a metastatic melanoma patient stimulated by Me1B6/B7 developed an higher lytic activity not only against Me1B6 but also against their autologous, B7-1^? tumor. Finally, after Me1B6/B7 stimulation, PBL released interleukin (IL)-2 and interferon-γ, but not IL-4, suggesting a Th1-mediated response. These data support the use of B7-1 transfected melanoma cells in the therapeutic vaccination of melanoma patients.     

Malformations of the axial skeleton in the museum Vrolik: II: craniosynostoses and suture-related conditions

The Museum Vrolik collection of anatomical specimens in Amsterdam, The Netherlands, comprises over 5,000 specimens of human and animal anatomy, embryology, pathology, and congenital anomalies. Recently, we rediagnosed a subset of the collection comprising dried infantile, juvenile, and adult human skulls with congenital and acquired conditions. On external examination and additional radiography, we found 58 skulls with craniosynostosis (CS) involving one or more sutures and 40 skulls with a presumed suture related condition. Most of these were part of the material collected and described by Louis Bolk (1866-1930). Analysis of his observations suggests that skull deformation because of premature suture closure depends not only on the identity of the sutures involved but also on the timing and progression of their closure and the extent of their involvement. Moreover, premature closure of the sagittal suture after 3-6 years of age appeared to be much more common than expected because it is not accompanied by skull deformation. Many of the skulls with single-suture CS were microcephalic, which may be the cause of the premature synostosis. By contrast, microcephaly may be a resulting phenomenon in multi-suture CS. We noticed that the quotient between height of the cranial vault (vertex-porion distance) and head circumference, multiplied by 100, was 26 or higher only in those CS cases with multi-suture involvement. We therefore consider this parameter, which we named "acrocephalic index", to be an indicator of multi-suture involvement in individual CS cases. In two adult skulls, the skull had a quadrangular shape, which we assumed to be correlated to the presence of an unusually interdigitated open metopic suture. We propose to name this anomaly: tetragonocephaly. Another presumed suture-related condition, bathrocephaly, was found concomitantly with basilar invagination in several cases. We hypothesize that the chronically raised intracranial pressure in these cases caused the still open lambdoidal sutures to distend and the occipital bone to protrude.     

Lymphopenia in acute nitrofurantoin pleuropulmonary reactions

Each of 5 patients with acute nitrofurantoin pleuropulmonary reactions had profound lymphopenia and 4 had eosinophilia developing early in the clinical course after the drug was withdrawn. The 2 patients tested had only one third of the normal numbers of E rosettes (T lymphocytes) in the peripheral blood during recovery. Lymphoblastic transformation tests with purified nitrofurantoin were done in 3 patients and all of them were negative; responses to phytohemagglutinin, concanavalin A, and pokeweed were decreased but still normal. The diagnosis of various nitrofurantoin hypersensitivity reactions relies on clinical data. The mechanisms of these reactions presently remain unclear.     

Spontaneous dissecting aneurysms of coronary arteries in a cardiac allograft

Dissecting aneurysms of coronary arteries are a rare finding and have never been reported in a cardiac allograft. We found two spontaneous dissecting aneurysms on the middle third of both the left anterior descending and the right coronary arteries in a female cardiac transplantation recipient. She died 43 days after cardiac transplantation after developing human cytomegalovirus pneumonia and pancreatitis. Dissecting coronary aneurysms, microfoci of subendocardial coagulative necrosis, and area of subepicardial dystrophic calcifications were discovered at necropsy examination.     

Telomerase reactivation is an early event in laryngeal carcinogenesis.

The exact role and timing of reactivation of telomerase, a key enzyme implicated in cellular immortalization and transformation in the multistep process of laryngeal carcinogenesis, is still unknown. We attempted to (1) determine that quantitative differences exist in the levels of telomerase catalytic subunit (hTERT) mRNA expression among different grades of laryngeal epithelial abnormalities classified according to the Ljubljana classification; (2) determine that telomerase reactivation is an important, most probably early event in laryngeal carcinogenesis; and (3) analyze whether the relative quantity of hTERT mRNA can be used as a molecular biomarker in the early detection of precancerous lesions. The relative quantity of hTERT mRNA, expressed as an hTERT index, was analyzed in 140 frozen laryngeal tissue specimens representing different morphological stages of laryngeal carcinogenesis by using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. The presence and relative quantity of hTERT mRNA in laryngeal epithelium increases progressively with the degree of epithelial abnormalities. hTERT mRNA was detectable in 1/15 normal laryngeal epithelia (7%, mean hTERT index 0.02), 3/15 simple hyperplasias (20%, mean hTERT index 0.09), 10/27 abnormal hyperplasias (37%, mean hTERT index 0.18), 9/12 atypical hyperplasias (75%, mean hTERT index 0.74), 8/9 intraepithelial carcinomas (89%, mean hTERT index 1.82), and 53/62 invasive laryngeal squamous cell carcinomas (85%, mean hTERT index 2.51). Statistical analysis revealed two groups of laryngeal epithelial changes with significant differences in the levels of hTERT mRNA expression (P <.0033): (1) normal and reactive hyperplastic laryngeal epithelium (simple and abnormal hyperplasia) and (2) atypical hyperplasia (precancerous lesion), intraepithelial and invasive laryngeal squamous cell carcinoma. The results of the present study suggest that telomerase reactivation is an early event in laryngeal carcinogenesis, detectable already at the stage of precancerous laryngeal epithelial changes. Nevertheless, other genetic abnormalities appear to be necessary for progression of these epithelial abnormalities toward invasive laryngeal squamous cell carcinoma.