Spinal paraparesis due to leukemic meningitis in early-stage chronic lymphocytic leukemia

Leukemic meningitis is a rare manifestation of chronic lymphocytic leukemia (CLL) and typically occurs in advanced stages. We report the case of a 71-year-old male in whom Binet A, Rai 1 stage CLL was diagnosed in June 2002. The stage called for a "watch and wait" strategy. Six months later the patient presented with paraparesis. Magnetic resonance imaging of the lumbar spine revealed no abnormalities. Lumbar puncture disclosed xanthochromic cerebrospinal fluid (CSF) with 1003 cells/microl, 95% atypical lymphocytes. Flow cytometry confirmed typical features of CLL. Intrathecal injections of methotrexate, cytosine arabinoside and corticosteroids did not substantially reduce the CSF cell count and failed to improve the neurological symptoms. Two weeks later the patient developed a pulmonary embolism complicated by fatal secondary pneumonia. Leukemic meningitis is a rare manifestation of CLL, especially in early stages. Selective spinal paraparesis as the first symptom of meningitis in CLL is even rarer and has been reported only once.     

Clinical trials targeting lung cancer with active immunotherapy: the scope of vaccines

Successful active immunotherapy is expected to be specific and nontoxic. Until now, the success of immunotherapy in cancer has been sporadic and unpredictable. This has been attributable in part to the lack of a full understanding of the mechanistic underpinnings of immune regulation. Furthermore, the lack of systematic success of immunotherapy, as argued in this review, stems from failing to effectively target tumors such as non-small cell lung cancer. In this review, the rationale and design for induction of immunity to non-small cell lung cancer and clinical trials of the most important lung cancer vaccines in development are discussed.     

Corneometric, sebumetric and TEWL measurements following the cleaning of atopic skin with a urea emulsion versus a detergent cleanser

A non-detergent urea emulsion cleanser and a detergent cleanser with added moisturizers were compared for their effects on stratum corneum moisture, surface lipids and transepidermal water loss (TEWL) of atopic skin. Following a single wash with either cleanser, low corneometry and sebumetry values increased and elevated TEWL values decreased. Over the course of more than 6 h, all induced changes gradually returned to their starting points. In all instances, the changes induced by the urea emulsion lasted significantly longer than those caused by the detergent cleanser. The sebumetry increase after a wash with the lipid-free detergent cleanser indicated that this method recognized not only true lipids but also the lipid-derived and skin lipid-depleting detergents. The transient TEWL normalization with either cleanser could not be attributed to a passing barrier restoration nor to an occlusion. It is speculated that the TEWL changes were related to stratum corneum water binding capacity.     

3He-MRI in follow-up of lung transplant recipients

The aim of this study was to evaluate the possible contribution of ³He-MRI to detect obliterative bronchiolitis (OB) in the follow-up of lung transplant recipients. Nine single- and double-lung transplanted patients were studied by an initial and a follow-up ³He-MRI study. Images were evaluated subjectively by estimation of ventilation defect area and quantitatively by individually adapted threshold segmentation and subsequent calculation of ventilated lung volume. Bronchiolitis obliterans syndrome (BOS) was diagnosed using pulmonary function tests. At ³He-MRI, OB was suspected if ventilated lung volume had decreased by 10% or more at the follow-up MRI study compared with the initial study. General accordance between pulmonary function testing and ³He-MRI was good, although subjective evaluation of ³He-MRI underestimated improvement in ventilation as obtained by pulmonary function tests. The ³He-MRI indicated OB in 6 cases. According to pulmonary function tests, BOS was diagnosed in 5 cases. All diagnoses of BOS were also detected by ³He-MRI. In 2 of these 5 cases, ³He-MRI indicated OB earlier than pulmonary function tests. The results support the hypothesis that ³He-MRI may be sensitive for early detection of OB and emphasize the need for larger prospective follow-up studies.     

Isolated pancreatic islets in three-dimensional matrices are responsive to stimulators and inhibitors of angiogenesis

The formation of a new microvasculature is essential for the long-term survival and function of the islet graft. In this study we examined endothelium of isolated pancreatic islets by stimulation with growth factors, different culture conditions, and genetic modification. We also inspected the effect of immunosuppressives used in human transplantation on angiogenesis. Isolated islets were embedded in a three-dimensional fibrin or Matrigel matrix. The effect of hyperglycemia, hypoxia, and the addition of VEGF and bFGF was investigated. We exposed islets from transgenic mice expressing the VEGF gene (RIP1VEGF-A) to high glucose (16.7 mmol/L) medium and tested the immunosuppressive agents rapamycin (100 ng/ml) and FK506 (100 ng/ml). To quantify angiogenesis the percentage of sprouting islets was determined. New endothelial capillary-like structures protruded from isolated pancreatic islets. Addition of VEGF to the islets and transgenic RIP-VEGF islets showed a two- to threefold increase of sprouting islets compared to control. Hypoxic culture conditions stimulated angiogenesis, resulting in a twofold increase of capillary sprouting. Rapamycin and FK506 proved to be potent inhibitors of angiogenesis in this system, because a decrease of sprouting islets of more than 20% by both agents was observed. Isolated pancreatic islets are capable of forming new capillary structures and are susceptible to pro- and antiangiogenic stimuli.     

A new ultrasensitive way to circumvent PCR-based allele distinction: direct probing of unamplified genomic DNA by solution-phase hybridization using two-color fluorescence cross-correlation spectroscopy

Single-molecule fluorescence methods enable a new class of nucleic acid assays to be performed that are not possible with PCR-based methods. In this basic study, the methylene tetrahydrofolate reductase (MTHFR)-genotypes (normal, homozygous mutated, as well as heterozygous mutated) were directly detected for the first time onto unamplified double-stranded genomic DNA in solution down to femtomolar allele concentrations (10(-15) M) in a homogeneous assay format. This was accomplished by taking advantage of the decrease by a factor of 40 to 100 in fluorescence background signals of the non-bound nonlinear hybridization probes in two colors and two-color fluorescence cross-correlation spectroscopy. The designed 'intelligent' probes contained the built-in 5'-fluorescent dyes rhodamine green and Alexa633, respectively, and the 3'-non-fluorescent quenchers BHQ1 and BHQ3, respectively, with perfectly matched spectral overlaps for both dye-quencher combinations. Upon binding of two appropriate probes that were sequence-specific for the genotype, the steady-state fluorescence in two colors increased by about two orders of magnitude. The obtained allele sensitivity of femtomolar and the specificity of the described molecular interactions allow PCR-based allele distinction to be circumvented. Furthermore, the results present an alternative to existing hybridization approaches that are currently used with and without amplification at the 'many-molecule' level and the 'single-molecule' level.     

Effects of feeding an infant formula containing Lactobacillus GG on the colonization of the intestine: a dose-response study in healthy infants

OBJECTIVES: This study aimed to determine whether feeding Lactobacillus GG (LGG) at varying levels (10 to 10 cfu/day) would result in colonization, defined as > or =1,000 cfu of LGG per gram of stool in 3 of 5 samples collected during the feeding period. METHODS: Infants received unsupplemented formula during a 7-day baseline, 1 of 4 formulas containing 0 (control), 10 (low), 10 (medium), or 10 (high) cfu of LGG per day during a 2-week test, and unsupplemented formula during a 2-week follow-up. Baseline, test, and follow-up stool samples were evaluated for levels of viable LGG. RESULTS: During test, supplemented infants were colonized, compared with control (P < 0.05). Median stool counts of LGG (log10 cfu/g) in colonized infants were 5.24 (low), 6.05 (medium), and 5.97 (high). LGG persisted in the stools for 7 to 14 days after discontinuing LGG. No differences were observed among groups in stool consistency, flatulence, fussiness, or adverse events. CONCLUSION: A 2-week oral administration of 10 to 10 cfu/day LGG was well tolerated; all levels successfully colonized the intestinal tract of healthy, term infants.     

Erfahrungen mit der Leukotomie bei den sogenannten „Zwangsneurosen“

Zusammenfassung Wir berichteten über 26 in unserer Klinik wegen Zwangssymptomatik psychochirurgisch behandelte Patienten.Zur Herausarbeitung einer differenzierten Indikationsstellung wurde unter Verwendung von in der Literatur üblichen Begriffen eine Einteilung unseres Krankengutes versucht. Es ergaben sich folgende Gruppen: Zwangsneurose, Zwangskrankheit, anankastische Psychopathie.Bei der Zwangsneurose waren die Erfolge der Leukotomie nicht überzeugend. Gute Ergebnisse waren bei der Zwangskrankheit zu verzeichnen. Bei jeder Form von Psychopathie halten wir die Leukotomie für kontraindiziert. Von den 14 Zwangskranken waren 11 anhaltend und 3 temporär subjektiv wie objektiv wesentlich gebessert.Auf die Wichtigkeit intensiver psychagogischer Nachbehandlung wurde hingewiesen.