Fluoroquinolone and beta-lactam antimicrobials induce different transcriptome profiles in Salmonella enterica persister cells.

Here, we investigate the transcriptome profiles of two S. Enteritidis and one S. Schwarzengrund isolates that present different persister levels when exposed to ciprofloxacin or ceftazidime. It was possible to note a distinct transcript profile among isolates, time of exposure, and treatment. We could not find a commonly expressed transcript profile that plays a role in persister formation after S. enterica exposure to beta-lactam or fluoroquinolone, as only three DEGs presented the same behavior under the conditions and isolates tested. It appears that the formation of persisters in S. enterica after exposure to ciprofloxacin is linked to the overexpression of genes involved in the SOS response (recA), cell division inhibitor (sulA), iron-sulfur metabolism (hscA and iscS), and type I TA system (tisB). On the other hand, most genes differentially expressed in S. enterica after exposure to ceftazidime appeared to be downregulated and were part of the flagellar assembly apparatus, citrate cycle (TCA cycle), glycolysis/gluconeogenesis, carbon metabolism, bacterial secretion system, quorum sensing, pyruvate metabolism pathway, and biosynthesis of secondary metabolites. The different transcriptome profiles found in S. enterica persisters induced by ciprofloxacin and ceftazidime suggest that these cells modulate their response differently according to each stress.

In vivo occupancy of dopamine D3 receptors by antagonists produces neurochemical and behavioral effects of potential relevance to attention-deficit-hyperactivity disorder.

Dopamine D(3) receptors have eluded definitive linkage to neurologic and psychiatric disorders since their cloning over 20 years ago. We report a new method that does not employ a radiolabel for simultaneously defining in vivo receptor occupancy of D(3) and D(2) receptors in rat brain after systemic dosing using the tracer epidepride (N-[[(2S)-1-ethylpyrrolidin-2-yl]methyl]-5-iodo-2,3-dimethoxybenzamide). Decreases in epidepride binding in lobule 9 of cerebellum (rich in D(3) receptors) were compared with nonspecific binding in the lateral cerebellum. The in vivo occupancy of the dopamine D(3) receptors was dose dependently increased by SB-277011A (trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl]cyclohexyl]-4-quinolinecarboxamide) and U99194 (2,3-dihydro-5,6-dimethoxy- N,N-dipropyl-1H-inden-2-amine). Both antagonists increased extracellular levels of acetylcholine (ACh) in the medial prefrontal cortex of rats and modified brain-tissue levels of ACh and choline. Consistent with these findings, the D(3) receptor antagonists enhanced the acquisition of learning of rats either alone or in the presence of the norepinephrine uptake blocker reboxetine as with the attention-deficit-hyperactivity disorder (ADHD) drug methylphenidate. Like reboxetine, the D(3) receptor antagonists also prevented deficits induced by scopolamine in object recognition memory of rats. Mice in which the dopamine transporter (DAT) has been deleted exhibit hyperactivity that is normalized by compounds that are effective in the treatment of ADHD. Both D(3) receptor antagonists decreased the hyperactivity of DAT(-/-) mice without affecting the activity of wild type controls. The present findings indicate that dopamine D(3) receptor antagonists engender cognition-enhancing and hyperactivity-dampening effects. Thus, D(3) receptor blockade could be considered as a novel treatment approach for cognitive deficits and hyperactivity syndromes, including those observed in ADHD.

Electropotential measurements as a new diagnostic modality for breast cancer.

BACKGROUND: Proliferative changes in breast epithelium are an intrinsic aspect in the development of breast cancer, and result in regions of epithelial electrical depolarisation within the breast parenchyma, which can extend to the skin surface. Diagnostic information might be obtained from a non-imaging and non-invasive test based on skin-surface electropotentials. METHODS: In 661 women, scheduled for open biopsy at eight European centres, we studied whether measurements of breast electrical activity with surface sensors could distinguish benign from malignant breast disease. A depolarisation index was developed. RESULTS: We found a highly significant trend of progressive electrical changes according to the proliferative characteristics of the biopsied tissue. Discriminatory information was obtained in both premenopausal and postmenopausal women, and the index was not related to age. The best test performances were for women with palpable lesions. The median index was 0.398 for non-proliferative benign lesions, 0.531 for proliferative benign lesions, and 0.644 for cancer (ductal carcinoma-in-situ and invasive). A specificity of 55% was obtained at 90% sensitivity for women with palpable lesions when a discriminant based on age and the depolarisation index was used. INTERPRETATION: This new modality may have diagnostic value, especially in reducing the number of unnecessary diagnostic tests among women with inconclusive findings on physical examination. Understanding and control of the biological variability of these electrical phenomena will be important in the improvement of this test. Studies in populations with a lower cancer prevalence are needed to assess further the diagnostic value of this approach.

Electropotential evaluation as a new technique for diagnosing breast lesions.

A new approach, termed the Biofield test, may have the potential to augment the process of diagnosing breast cancer. This technique is based on the analysis of skin surface electrical potentials measured by an array of specially designed sensors which are placed on the breasts. Measurements are recorded noninvasively and then analyzed using pattern recognition algorithms to produce an immediate and objective assessment of breast tissue in vivo. Initial clinical trials suggests that the test can achieve a sensitivity of approximately 90% and a specificity of 40-50%, which indicates that the test might be useful for excluding cancer when it is, in fact, absent. Although research to date has focused on the differential diagnosis of suspicious breast lesions, future applications could include breast cancer screening, close surveillance and diagnosis of recurrent cancers in breasts previously treated with conservative therapy, and monitoring the effectiveness of breast cancer therapies. Improvements and new applications are expected to occur as additional research and validation in actual clinical settings is performed.

Cardiac microembolism: prevalence and clinical outcome.

High intensity transient signals (HITS) have been identified ultrasonically in patients with extracranial vascular or cardiac disease and are suggestive of microembolic material. We studied the prevalence of these signals in 60 patients with increased risk for cardioembolic stroke and in a control group of 20 subjects. Patient groups (n = 20) were characterized by either non-rheumatic atrial fibrillation (AFIB) (I) or a history of prosthetic valve surgery with AFIB (II) or without AFIB (III). Embolic signals were not seen in the control group. In group I, 3 patients (15%) demonstrated HITS, in groups II and III 10 patients (50%). Microembolic signals in patients with prosthetic heart valves (II, III) had a higher signal intensity, indicating different embolic material. There was no correlation of microembolic signals with the anticoagulant treatment or the position of the prosthetic valve. HITS were found in 1/9 (11%) of the patients with a bioprosthetic valve as compared to 19/31 (61%) with a mechanical valve. After 6-12 months, 1 of 12 HITS positive patients had experienced a stroke and 2 had died. None of the 28 patients without HITS had suffered a stroke, 2 had died. Microembolic signals are frequent events in patients with mechanical prosthetic valves. In these patients they do not appear to be a major prognostic factor for an impending cardioembolic stroke.

[Effects of chemotherapy and radiotherapy of malignant testicular tumors on residual testicular tissue]. / Auswirkungen der Chemotherapie und Strahlentherapie von malignen Hodentumoren auf das verbliebene Hodengewebe.

By morphologic and morphometric investigations of the residual testis after treatment of testicular cancer the deleterious effect of chemo- and radiotherapy are estimated. Approximately 4-5 years after treatment the reversibility of spermatogenesis is better in patients chemotherapy than in patients after radiotherapy.

[Changes in serum hormones and the spermiogram in patients with malignant testicular tumors following radiation and cytostatic drug therapy]. / Serumhormone und Spermiogrammveränderungen bei Patienten mit malignen Hodentumoren nach Strahlen- und Zytostatikatherapie.

In 53 patients suffering from testicular cancer it was reviewed whether the changes of spermatogenesis due to radiation or chemotherapy are reflected by the sexual hormones (FSH, LH, T). After both therapeutic measures a reduction of the number of spermatic cells and volume of sperm was demonstrated. The reduction of spermatic cells was followed by a simultaneous increase of FSH and LH levels, whereas the testosterone level did remain normal.

[Retrograde ejaculation as a cause of aspermia following retroperitoneal lymph node excision and the effective use of alpha sympathomimetic drugs]. / Retrograde Ejakulation als Ursache der Aspermie nach retroperitonealer Lymphonodektomie und der wirkungsvolle Einsatz von Alpha-Sympathikomimetika.

Retroperitoneal lymphadenectomy may produce in the majority of patients an irreversible loss of normal ejaculation due to lesion of presacral sympathetic nerve fibers. Libido and orgasm did remain unchanged. In 14.3% of the patients a retrograde ejaculations could evaluated. By application of alpha-sympathicomimetic drugs this could reversed to an antegrade ejaculation. However, fertility was altered strongly because of motility loss.

[Diagnosis of breast carcinoma: "Mammography and additive methods"]. / Diagnostik des Mammakarzinoms: "Mammographie und additive Methoden".

Review about diagnostic methods in breast cancer with special reference to mammography. Comparison about the accuracy of mammography, fine needle biopsy, clinical investigation, electron thermography and plate thermography.

[Study of procreation capacity of men after treatment of their malignant tumors (melanoblastoma, thyroid carcinoma) with ionizing radiation and cytostatic agents]. / Untersuchung zur Zeugungsfähigkeit von Männern nach Therapie ihrer malignen Tumoren (Melanoblastome, Schilddrüsenkarzinom) mit ionisierenden Strahlen und Zytostatika.

5 patients suffered from melanoblastoma or thyroid cancer were treated with irradiation and cytostatics. The results of spermiograms before, and after treatment show with regard to fertility a moderate prognosis.

[Comparative histological studies of germinative tissue after chemotherapy or radiation therapy in patients with malignant testicular tumors]. / Vergleichende histologische Untersuchungen am germinativen Gewebe nach der Chemo- bzw. Strahlentherapie bei Patienten mit malignen Hodentumoren.

Described in this paper are morphological and morphometric alterations that occurred to the remaining testicles in patients who had undergone chemotherapy or radiotherapy for malignant testicular tumours, with findings, on average, being recorded 4.5 years after treatment. Qualitative histological investigations of testicular tissue exhibited differentiated characteristics, with radiotherapy resulting in significantly stronger phenomena. Epithelial height was clearly reduced in conjunction with increase in wall thickness, especially after radiotherapy. Tubular lumens, in the wake of radiotherapy, were more often filled with hyalin than after chemotherapy. Unambiguous evidence was produced to impairment of fertility in response to both chemotherapy and radiotherapy.

[Dependence of serum hormones (T, FSH, LH) on morphometric testicular findings after chemo- and radiotherapy in patients with malignant testicular tumors]. / Abhängigkeit der Serumhormone (T, FSH, LH) vom morphometrischen Hodenbefund nach Chemo- und Strahlentherapie bei Patienten mit malignen Hodentumoren.

Correlations which exist between morphometric parameters of remaining testicular tissue, on the one hand, and serum hormones on the other (testosterone = T, follicle-stimulating hormone = FSH, luteinising hormone = LH), depending on therapeutic action taken on patients for malignant testicular tumours, seem to suggest that decline in epithelial thickness together with increase in wall thickness leads to rise in FSH. No unambiguous relations, on the other hand, were found to exist between testosterone or luteotrophic hormone and morphometric findings. Hence, FSH seems to characterise the severity of damage to germ epithelium and thus the degree of impairment to spermatogenesis. FSH may be accepted as a criterion for fertility disorders in sexually active men.

[Assessment of visual acuity in simulation and aggravation]. / Zur Einschätzung der Sehschärfe bei Simulation und Aggravation.

Following a review of various tricks and techniques described in the literature for measuring the visual acuity of less cooperative patients, three new methods are presented. The first is based on the so-called "preferential-looking" method, which has been in use for several years to determine the visual acuity of infants and small children. The second method uses polarizing filters to separate the beam paths of the two eyes and a flashlamp to project the test symbols, to prevent the patient from finding out by blinking which eye is being tested. In the third method the stimuli are presented on a computer monitor; the beam paths of the two eyes are separated by special spectacles which can briefly cover either eye while a test symbol is being shown. The results so far are encouraging.

[Determining the diagnosis--tumor of the kidney pelvis--using sonography]. / Die Diagnosestellung--Nierenbeckentumor--mittels Sonographie.

The advantages and deficiencies of diagnostic imaging procedures especially of ultrasonography in the diagnostics of solid masses in the renal collecting system are presented. The intravenous urography is important as basic examination, but ultrasonography is valuable for additional information especially in the non-functioning kidney. A tumor could identified in the renal collecting system if its size is greater than 10 mm.

[Bilateral testicular tumors and the value of control sonography in the follow-up period]. / Bilaterale Hodentumoren und die Wertigkeit der Kontrollsonographie in der Nachuntersuchungsperiode.

With 4 cases of bilateral testicular tumors during a follow-up period of 10 years the importance of regular controls is stressed. The testis should examined routinely using high-frequency scanner for suspected intratesticular tumors. In 4 patients the diagnosis of the second tumor was made by close-meshedly controls using ultrasonography.

[Fertility studies in malignancy (tumors of the testicle, malignant melanomas, cancer of the thyroid gland)]. / Fertilitätsuntersuchungen maligner Tumoren (Hodentumoren, maligne Melanome, Schilddrüsenkarzinom).

The examination of 83 patients suffering from tumours (78 tumours of the testicle, 4 melanoblastomas, 1 carcinoma of the thyroid gland) led to conclusions on the effect of complex therapy on spermiogenesis. By means of spermiograms carried out in the course of the illness we found out restrictions of fertility which were more distinctly marked with patients suffering from gonadal tumours than with patients suffering from extragonadal tumours. The loss in ejaculation after RLN with existing tumours of the testes has to be considered as a disturbance in fertility to the highest degree. X-ray therapy impairs spermiogenesis more than chemotherapeutics. After chemotherapy we observed a recovery of spermiogenesis, after x-ray therapy only then if there were no irreversible damages of the germinal epithelium.

[Differential diagnosis of chronic peripancreatic pseudocysts on the computerized tomogram. Possibility of error and pitfalls]. / Differentialdiagnose der chronischen peripankreatischen Pseudozyste im Computertomogramm. Fehlermöglichkeiten und Fallgruben.

Cystic masses within the pancreas and in its neighbourhood are often really pseudocysts. In most cases, centrally necrotic solid tumours or genuine cystic neoplasms are easy to differentiate from such pseudocysts. They are in fact rare pathologic conditions. The exclusion of a pseudocyst is sometimes more difficult, especially in peripancreatic cystic masses. Computed tomography has significantly improved the diagnostics of the upper abdomen. Nevertheless, it sometimes creates new problems. This study is a selection of cases pointing to differential diagnostic difficulties that may become pitfalls for the examiner. An image-imminent approximative diagnosis is attempted. The importance of the localisation of these lesions and of the topographical anatomy of the upper abdomen are pointed out.