Genomic Dissection of Travel-Associated Extended-Spectrum-Beta-Lactamase-Producing Salmonella enterica Serovar Typhi Isolates Originating from the Philippines: a One-Off Occurrence or a Threat to Effective Treatment of Typhoid Fever?

One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring bla_SHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi.     

Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.     

Seeing Double: Annular Diaper Rash in Twins

We report a case of dichorionic, diamniotic twins who developed similar erythematous, annular, erosive plaques in the inguinal folds in the first few weeks of life that were refractory to topical antifungals and oral antibiotics. The twins were found to have high transaminase levels, antinuclear antibody positivity, and anti‐SSS/Ro) and anti‐SSB/La autoantibodies. The rash resolved without scarring by 7 months of age with the use of low‐potency topical corticosteroids. We suggest that physicians consider neonatal lupus erythematosus in neonates with atypical eruptions occurring in sun‐protected skin.     

Assessment of toxicity using dehydrogenases activity and mathematical modeling

Dehydrogenase activity is frequently used to assess the general condition of microorganisms in soil and activated sludge. Many studies have investigated the inhibition of dehydrogenase activity by various compounds, including heavy metal ions. However, the time after which the measurements are carried out is often chosen arbitrarily. Thus, it can be difficult to estimate how the toxic effects of compounds vary during the reaction and when the maximum of the effect would be reached. Hence, the aim of this study was to create simple and useful mathematical model describing changes in dehydrogenase activity during exposure to substances that inactivate enzymes. Our model is based on the Lagergrens pseudo-first-order equation, the rate of chemical reactions, enzyme activity, and inactivation and was created to describe short-term changes in dehydrogenase activity. The main assumption of our model is that toxic substances cause irreversible inactivation of enzyme units. The model is able to predict the maximum direct toxic effect (MDTE) and the time to reach this maximum (T_MDTE). In order to validate our model, we present two examples: inactivation of dehydrogenase in microorganisms in soil and activated sludge. The model was applied successfully for cadmium and copper ions. Our results indicate that the predicted MDTE and T_MDTE are more appropriate than EC₅₀ and IC₅₀ for toxicity assessments, except for long exposure times.     

78. Die Verwendung automatischer Nahtger?te in der Lungenchirurgie

Zusammenfassung Anhand von 678 bis Ende 1979 operierten Patienten mit Lungenerkrankungen wird die technische Anwendung automatischer Nahtgeräte demonstriert. Sie eignen sich zum Bronehusverschluß, für Keilexcisionen sowie zum Verschluß von Lungenvenen. Technische Modalitäten sind zu beachten. Der Vorteil liegt bei sachgemäßem Vorgehen in der Sicherheit der Anwendung, der Effektivität und in der kürzeren Operationszeit. Die Insuffizienzquote beträgt einschl. der Anfangszeit 4,4% in der Spätphase 3,2%. Komplikationen bei Keilexcisionen treten ebensowenig auf wie beim Verschluß der Lungenvenen.     

Resuscitation with Recombinant Hemoglobin rHb2.0 in a Rodent Model of Hemorrhagic Shock

Background: Hemoglobin solutions combine volume effect, oxygen-carrying capacity, and vasoactive properties, the latter facilitating restoration of global hemodynamics but endangering microvascular resuscitation. Hemoglobin-evoked vasoconstriction probably is due to nitric oxide scavenging, which can be reduced by genetic modifications of the heme pocket. This study compares resuscitation with a nonhemoglobin colloid and two recombinant hemoglobin solutions with wild-type and reduced nitric oxide-scavenging capacity.

Methods: Twenty-seven awake Syrian golden hamsters fitted with dorsal skinfold chambers underwent a 30 min-hemorrhagic shock (mean arterial pressure [MAP] 30-35 mmHg) and resuscitation with shed blood volume of either 6% dextran 60 (Biophausia, Uppsala, Sweden), recombinant hemoglobin 1.1 (rHb1.1; wild-type nitric oxide-scavenging capacity; 10 g/dl), or recombinant hemoglobin 2.0 (rHb2.0; reduced nitric oxide-scavenging capacity; 10 g/dl; both Baxter Healthcare, Boulder, CO). Macrohemodynamic and laboratory parameters were assessed; microvascular parameters in the skinfold chamber were analyzed by intravital microscopy.

Results: Hemorrhagic shock reduced functional capillary density (FCD) by 70% and caused significant metabolic acidosis. Colloid resuscitation led to incomplete recovery of MAP and FCD. Infusion of rHb1.1 completely restored MAP but not FCD, with the smallest arteriolar diameters found in this group. FCD was restored best by resuscitation with rHb2.0, although MAP was lower than in rHb1.1-treated animals. Metabolic acidosis was resolved by both hemoglobin solutions, but not by dextran.     

Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations

We analyzed 11 consecutive unrelated cases of polyneuropathy due to transthyretin amyloidosis. Direct sequencing of the promoter region, exons, and splice junctions revealed that each patient was heterozygous for a mutation: six patients had valine 30 substituted by methionine (V30----M; Portuguese-Japanese type), one had threonine 60 substituted by alanine (T60----A; Appalachian type), and two had serine 77 substituted by tyrosine (S77----Y; Illinois type). In addition, two patients had previously undescribed mutation: phenylalanine 33 substituted by leucine (F33----L) and phenylalanine 64 substituted by leucine (F64----L). From present information, the probands of these novel mutations do not exhibit any pathology that clearly distinguishes them from individuals with the other mutations. The mutations extend the range of mutations associated with amyloidotic polyneuropathy. In our 11 patients, the different mutations did not seem to correlate with distinct clinical phenotypes. We developed PASA assays (PCR amplification of specific alleles) for each of the five mutations. PASA can be used by any diagnostic laboratory that can perform PCR to rapidly detect any of the known mutations. The minority of samples with an undescribed mutation can be sent to a specialty laboratory for delineation of the mutation by direct genomic sequencing. The presently described combination of methods may have widespread utility in the diagnosis of genetic disease.     

Genetic Analyses of the Mouse Deafness Mutations Varitint-Waddler (Va) and Jerker (Espnje)

Genetic studies on spontaneous mouse mutants with hearing defects have provided important insights into the function of genes expressed in inner ear hair cells. Here we report on our genetic analyses of the deaf mutants varitint-waddler (Va) and jerker (Espnje). A high-resolution genetic map localizes VaJ to a 0.14 ± 0.08 cM region between D3Mit85 and D3Mit259 on distal chromosome 3. By comparative mapping, the human ortholog resides at 1p22.3 between markers D1S3449 and D1S2252. To study the effect of different genetic backgrounds on the hearing phenotype, Espnje and VaJ were crossed to various inbred strains. Auditory-evoked brainstem response tests on F2 progeny demonstrate that expression, inheritance, and penetrance of the hearing phenotype are solely controlled by the mutant allele. To test for a genetic interaction between Espnje and Cdh23v, auditory function was analyzed in double heterozygotes; no significant increases of thresholds of sound pressure levels were observed. The results establish the framework for cloning the Va gene and provide valuable insights into the genetics of deafness mutations in the mouse.