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Biomedical subjects

S Roth

Publications and source records attributed to S Roth.

At least 109 records · Page 6Linked to original sources

Revision of nonfunctioning kock pouch efferent limb: continent, tissue preserving technique.

PURPOSE: Despite extensive surgical experience with the intussuscepted efferent nipple of the Kock pouch, complications are not unusual. Although most repairs are relatively simple, the use of intestinal segments is necessary for reconstruction of the complete efferent limb in cases of severe stenosis, pre-stenotic diverticular enlargement or partial necrosis. We describe the tissue preserving transformation of an inadequate efferent Kock pouch outlet into a flap-valve continence mechanism. MATERIALS AND METHODS: In 5 women a new efferent limb for the Kock pouch was created by transverse retubularization of the short intact ileal segment of the original limb. Continence was preserved through the construction of a Mitrofanoff-like flap valve, created by embedding the new ileal tube in an extramural trough. RESULTS: At followup ranging from 6 to 28 months all patients were continent and experienced no problems with catheterization. CONCLUSIONS: This technique of transverse retubularization of the inadequate efferent ileal limb and creation of a flap valve has obvious advantages. No new small bowel segments are required, thereby simplifying and shortening the procedure. The newly created ileal tube is wide (16 to 18Fr) and easy to catheterize. The mucosal folds are longitudinal and do not impede catheterization. The remaining thin layer of mesentery is set in the center of the tube and permits construction of a straight extramural tunnel.

Adult↗

Encephalopathy with epileptic spasms resolved with corticoids in a 69 year-old patient.

A 69 year-old man with a history of recent temporal lobe seizures, presented with progressive coma and frequent epileptic spasms. Ictal EEG, PET and SPECT alterations were strikingly similar to those described in infantile spasms. Conventional antiepileptic drugs were ineffective but the introduction of corticoids induced a dramatic improvement with disappearance of the spasms. The etiology remains unknown. Epileptic spasms may occur in the elderly. If conventional antiepileptic drugs are ineffective, corticoids should be tried immediately.

Aged↗

Carbon nanotube actuators

Electromechanical actuators based on sheets of single-walled carbon nanotubes were shown to generate higher stresses than natural muscle and higher strains than high-modulus ferroelectrics. Like natural muscles, the macroscopic actuators are assemblies of billions of individual nanoscale actuators. The actuation mechanism (quantum chemical-based expansion due to electrochemical double-layer charging) does not require ion intercalation, which limits the life and rate of faradaic conducting polymer actuators. Unlike conventional ferroelectric actuators, low operating voltages of a few volts generate large actuator strains. Predictions based on measurements suggest that actuators using optimized nanotube sheets may eventually provide substantially higher work densities per cycle than any previously known technology.

Journal Article↗

The Drosophila gene brinker reveals a novel mechanism of Dpp target gene regulation.

decapentaplegic (dpp), a Drosophila member of the TGFbeta family of secreted molecules, functions as a long-range morphogen in patterning of the embryo and the adult appendages. Dpp signals via the SMAD proteins Mad and Medea. Here we show that in the absence of brinker (brk), Mad is not required for the activation of Dpp target genes that depend on low levels of Dpp. brk encodes a novel protein with features of a transcriptional repressor. brk itself is negatively regulated by Dpp. Dpp signaling might relieve brk's repression of low-level target genes either by transcriptional repression of brk or by antagonizing a repressor function of brk at the target gene promoters.

Animals↗

SMAD genes in juvenile polyposis.

Juvenile polyposis (JP) is a dominantly inherited condition characterized by the development of multiple hamartomatous tumors, juvenile polyps, in the gastrointestinal tract. The aim of this study was to clarify the role of SMAD4 in JP. DNA from four unrelated JP kindreds and three sporadic JP cases was available for mutation screening. Two truncating defects (one in a familial and one in a sporadic case) and one missense change (in a familial case) that was absent in 55 control samples were detected. To study the possibility that germline mutations in other genes encoding different components of the TGF-beta signaling pathway may be present in these JP patients, mutation analyses of the SMAD2, SMAD3, and SMAD7 genes were also performed. No mutations of these genes were detected in any of the patients. Our results confirm that SMAD4 is a gene predisposing to JP and suggest the existence of further JP loci other than the SMAD2, SMAD3, or SMAD7 genes. Genes Chromosomes Cancer 26:54-61, 1999.

Adenomatous Polyposis Coli↗

A biological role for deletions in chromosomal band 13q14 in mantle cell and peripheral t-cell lymphomas?

Structural aberrations of chromosomal band 13q14 are frequent in B-cell chronic lymphocytic leukemia (B-CLL) and target a putative tumor suppressor gene in the genomic region between the RB1 gene and the genetic marker D13S25. Recently, it has been suggested that alterations of this particular region might also be of relevance for the pathogenesis of mantle cell lymphomas (MCL). We applied dual-color fluorescence in situ hybridization (FISH) using probes for the RB1 and/or D13S25 loci and screened a total of 236 B- and T-cell non-Hodgkin's lymphomas (NHL) for deletions occurring in this genomic region. In MCL, the high rate (12/32; 38%) of hemizygous deletions and especially a deletion pattern similar to B-CLL in four of the cases provide further evidence that a substantial proportion of MCL cases may share a common way of pathogenesis with B-CLL. In other B-cell NHL, the frequency of allelic loss affecting 13q14 was overall low. However, the finding of 13q14 microdeletions in seven cases without detectable alterations of chromosome 13 at G-banding analysis might indicate a possible involvement of this genetic region also for the lymphomagenesis of single cases of B-cell NHL other than B-CLL and MCL. In T-cell NHL, allelic loss at 13q14 was encountered in three of 13 peripheral T-NHL, NOS. Taking into account the very limited cytogenetic data yet available in this entity, our series provides further evidence that 13q14 changes might represent one of the most frequent genetic abnormalities in T-cell NHL.

Chromosome Banding↗

Differing roles of adenosine receptor subtypes in retinal ischemia-reperfusion injury in the rat.

Adenosine has been shown to be a major component of the retina's endogenous reaction to ischemia. In earlier studies, the significant changes in adenosine concentration that occur during ischemia and the ensuing reperfusion period were documented. While previous studies have shown that adenosine is a mediator of the changes in blood flow that occur in response to ischemia, hypoxia, and hypoglycemia in the retina, little is known about other functional effects that result from these changes in adenosine concentration. Accordingly, the influence of adenosine receptor blockade on the functional and histological outcome following ischemia in rats was examined. Specific antagonists of the adenosine A1 and A2a receptors were injected systemically, prior to ischemia of either 5, 30, or 60 min. The recovery of the electroretinogram a and b waves was followed for up to 7 days after ischemia, and retinal structure was examined by light microscopy. The adenosine A1 receptor antagonist DPCPX attenuated recovery after retinal ischemia of either 5 or 30 min, while the A2a receptor antagonist CSC dramatically protected retinal function and structure even with ischemia lasting up to 60 min. It was concluded that blockade of the A2a receptor, possibly combined with stimulation of the A1 receptor, may represent a potential new strategy for the prevention of ischemic damage in the retina.

Animals↗

[Pilot study on early diagnosis of renal cell carcinoma by sonography].

UNLABELLED: The goal of this study was to investigate the practicability and effectiveness of a systematic screening for renal cell carcinoma by ultrasound in the course of the established German Health Ministry screening programs. METHODS: In two centers (Mainz and Wuppertal) a screening program for renal cell carcinoma for all citizens (age > 40 years) was established. The screening was divided into two phases (time period 1 year): (1) All citizens over 40 years could attend voluntarily a cost-free ultrasound investigation. (2) A follow-up investigation for the entire screening population was provided. RESULTS: Ten thousand volunteers attended the screening program. Mean age was 60 years. Thirteen renal cell carcinomas were detected. The incidence of other findings was 15%; none of those required further treatment. CONCLUSION: Systematic screening for renal cell carcinoma by ultrasound is cost-effective and showed high acceptance and practicability in a German population. The rate of detection of renal cell carcinoma was higher than initially statistically calculated.

Aged↗

[Regeneration of mouth mucosa in the buccal plane following graft procurement for reconstruction of bulbar urethral stenoses].

The use of free buccal mucosal grafts in the treatment of urethral strictures has become very popular. In 1996 and 1997 we harvested free buccal mucosal grafts up to 7 cm long and 4 cm wide from 12 patients who underwent urologic surgery for urethral strictures. In 2 patients the donor site was closed primarily by sutures. Four patients received Lyodura and another 4 patients received Syspurderm as temporary wound coverage. In 2 patients Ethisorp patches were used. Donor site pain was judged by the patients on a visual analogue scale during the first postoperative week. The 2 patients who received the Ethisorp patches complained of more intense pain, probably caused by the rigidity of the material. In all patients regeneration of the donor site mucosa was good. During the follow-up period of 4-18 months scar formation at the lower vestibulum was noticed as the only complication. Permanent limitation of mouth opening, stenosis of the parotid duct or hypesthesia did not occur.

Adolescent↗

LKB1 somatic mutations in sporadic tumors.

Germline mutations of LKB1/Peutz-Jeghers syndrome gene predispose carriers to hamartomatous polyposis of the gastrointestinal tract as well as to cancer of different organ systems. Although Peutz-Jeghers syndrome patients frequently present with neoplasms of the colon, stomach, small intestine, pancreas, breast, ovaries, and cervix, somatic mutations appear to be rare in the sporadic tumor types thus far studied (colorectal, gastric, testicular, and breast cancers). To evaluate whether somatic mutations of LKB1 contribute to the tumorigenesis of yet unstudied tumor types, we screened 14 cell lines and 129 tumor specimens from different cancers for a genetic defect in LKB1. Six melanoma and eight myeloma cell lines were scrutinized for LKB1 somatic mutations by genomic sequencing. No changes were found in the coding LKB1 sequence and exon/intron boundaries. Next, we analyzed 12 pancreatic, 8 gastric, 12 ovarian granulosa cell, 26 cervical, 28 lung, 24 soft tissue, and 19 renal tumors by single-strand conformational polymorphism analysis. Three changes in LKB1 coding nucleotide sequence were identified. One base pair deletion at A957 and G958 substitution by T occurred in a cervical adenocarcinoma sample, resulting in a frameshift and premature stop codon at position 335. Substitution of A581 by T occurred in a lung adenocarcinoma sample, resulting in the change of aspartic acid at position 194 to valine. A loss of another allele was detected in this sample. One silent change, C1257T, was found in a pancreatic carcinoma sample. The changes were not present in the matched normal tissue DNA samples. Our results suggest that mutational inactivation of LKB1 is a rare event in most sporadic tumor types.

AMP-Activated Protein Kinase Kinases↗

The purine nucleoside adenosine in retinal ischemia-reperfusion injury.

Adenosine, an intercellular messenger that is a product of the metabolism of ATP, plays a major role in neuronal and vascular responses of the retina to alterations in oxygen delivery. Significant changes in adenosine concentration have been measured in the retina during both ischemia and during the subsequent reperfusion period which result in important, but complex, functional effects. Adenosine A1 receptor stimulation produces a protective effect during ischemia, whereas overstimulation of the A2a receptor has deleterious effects. The mechanisms underlying these findings have not been completely determined, but most likely are the result of alterations in excitotoxicity, gene expression, and blood flow. Paradoxically, prolonged increases in adenosine concentration may be injurious to the retina, a consequence of superoxide radical formation secondary to adenosine catabolism. Adenosine is a critical mediator of blood flow changes in response to ischemia. It is a significant component of the retina's compensatory hyperemic response to ischemia, hypoxia, and hypoglycemia. Increasing endogenous adenosine concentrations may be useful in ameliorating post-ischemic hypoperfusion. Overall, current evidence suggests that adenosine is a vital component of the endogenous retinal response to substrate deprivation. Additionally, in vitro studies provide strong evidence that adenosine is a mediator of the formation and effects of vascular endothelial growth factor, which in turn promotes neovascularization. Finally, the ability of the retina to develop an ischemia-tolerant state by ischemic preconditioning is an intriguing phenomenon that reveals yet another essential role for adenosine in the retina's endogenous response to ischemia. The experimental results described in this review suggest that continued investigation into the role of adenosine in the retina may lead to important clinical applications for adenosine-based therapies that could decrease the incidence of retinal damage in ischemic vasculopathies such as diabetes, glaucoma, and retinal vascular occlusion.

Adenosine↗

Febrile lady with acute renal failure and desquamating erythema.

A 63-year-old woman developed acute renal failure and streptococcal toxic shock syndrome caused by streptococcus group G. Initially, an erythema resembling vasculitis was misleading. The subsequent clinical course, however, was typical for streptococcal toxic shock syndrome and met the criteria put forward by The Working Group on Severe Streptococcal Infections. In patients infected with streptococcus group G, toxic shock syndrome is rare. The streptococcus group G strains isolated from this patient did not produce pyrogenic exotoxins. Instead they produced an M-like protein related to group C and G streptococci that do not act as superantigens.

Acute Kidney Injury↗

The neurodevelopmental outcome of term infants with different intrauterine growth characteristics.

The objective of this study was to test the hypothesis that neurodevelopmental outcome would differ between two groups of small-for-gestational age infants born at term showing different in utero growth characteristics during the third trimester. The design was a prospective cohort study done at a tertiary referral centre. The 76 subjects who fulfilled the inclusion criteria had an estimated fetal weight below the 10th centile for their gestation. Subsequent to enrolment, repeat ultrasound scans were performed weekly to determine growth velocity. Twenty-three infants whose change in fetal abdominal circumference between first and last scan was greater than -1.5 standard deviation scores (SDS) were assigned to the intrauterine growth retardation group (IUGR) while 53 infants whose fetal abdominal circumference changed less than 1.5 SDS were assigned to the small-for-gestational-age (SGA) group. Ten infants with normal intrauterine growth were enrolled as controls. Following delivery all infants had a neurological examination and a cranial ultrasound scan. At 1 year, 75 infants (87%) were traced and reassessed (49 SGA, 18 IUGR and eight controls) with a neurological examination and a developmental assessment. At birth, impairments were found in 27 (51%) of the SGA, 13 (57%) of the IUGR groups and one (10%) of the controls. At 1 year, 18 (37%) of the SGA subjects, six (33%) of the IUGR subjects and one (13%) of the control infant were impaired, including three (6%) of the SGA subjects and one (6%) of the IUGR subjects who were disabled. We conclude that in term fetuses with an estimated birthweight below the 10th centile for their gestation, the pattern of growth in the third trimester does not affect outcome at 1 year. In spite of optimum obstetric management, nearly one-third of the combined SGA and IUGR term fetuses had suffered some, albeit minor, neurological damage.

Apgar Score↗

Local Gurken signaling and dynamic MAPK activation during Drosophila oogenesis.

During Drosophila melanogaster oogenesis Gurken, a TGF-alpha like protein localized close to the oocyte nucleus, activates the MAPK cascade via the Drosophila EGF receptor (DER). Activation of this pathway induces different cell fates in the overlying follicular epithelium, specifying the two dorsolaterally positioned respiratory appendages and the dorsalmost cells separating them. Signal-associated internalization of Gurken protein into follicle cells demonstrates that the Gurken signal is spatially restricted and of constant intensity during mid-oogenesis. At the same time MAPK activation evolves in a spatially and temporally dynamic way and resolves into a complex pattern that presages the position of the appendages. Therefore, different dorsal follicle cell fates are not determined by a Gurken morphogen gradient. Instead they are specified by secondary signal amplification and refinement processes that integrate the Gurken signal with positive and negative feedback mechanisms generated by target genes of the DER pathway.

Animals↗

Toll homologue expression in the beetle tribolium suggests a different mode of dorsoventral patterning than in drosophila embryos.

The gene Toll (Tl) encodes a maternally supplied interleukin 1 receptor-related transmembrane protein, a key component required to establish dorsoventral polarity in the Drosophila embryo. We have isolated Tl homologs of a primitive dipteran, Clogmia albipunctata, and of the beetle Tribolium castaneum. Tribolium Tl protein (Tl) lacks sequences in the C-terminal portion of the cytoplasmic domains that are conserved in the dipteran homologs. The Tl homolog of Tribolium mediates the ventralizing activity when expressed as a gain-of-function variant in transgenic Drosophila, indicating that the sequences conserved in the Diptera are not essential for Tl signaling. In contrast to Drosophila where Tl gene expression occurs maternally and supplies uniformly distributed Tl in the egg membrane, Tl transcripts form a ventral-to-dorsal gradient in the Tribolium blastoderm stage embryo. This localized expression pattern of Tl transcripts, as compared with the strong maternal and ubiquitous expression in Drosophila and Clogmia embryos, suggests that dorsoventral patterning in long-germ band and short-germ band insects involves the same components but different modes of their action.

Amino Acid Sequence↗

Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer.

Germline mutations in LKB1 have been reported to underlie familial Peutz-Jeghers syndrome (PJS) with intestinal hamartomatous polyps and an elevated risk of various neoplasms. To investigate the prevalence of LKB1 germline mutations in PJS more generally, we studied samples from 33 unrelated PJS patients including eight non-familial sporadic patients, 20 familial patients and five patients with unknown family history. Nineteen germline mutations were identified, 12 (60%) in familial and four (50%) in sporadic cases. LKB1 mutations were not detected in 14 (42%) patients, indicating that the existence of additional minor PJS loci cannot be excluded. LKB1 is predicted to encode a serine/threonine kinase. To demonstrate the putative Lkb1 kinase function and to study the consequences of LKB1 mutations in PJS and sporadic tumors, we have analyzed the kinase activity of wild-type and mutant Lkb1 proteins. Interestingly, while most of the small deletions or missense mutations resulted in loss-of-function alleles, one missense mutation (G163D) previously identified in a sporadic testicular tumor demonstrated severely impaired but detectable kinase activity.

AMP-Activated Protein Kinase Kinases↗

Self-administered medication packet for patients experiencing a vaginal birth.

A patient satisfaction survey at Missouri Baptist Medical Center revealed that patients experiencing a vaginal delivery needed to wait for their medications and did not consistently receive adequate information about medications. Furthermore, a chart review noted that physicians ordered a wide variety of medications for their patients but that the patients did not always use all their medications. A review of patients' accounts determined that their medications were costly. A multidisciplinary team using the FOCUS-PDCA quality improvement model designed and implemented a self-administered medication packet. Outcomes included continued patient satisfaction with decreases in cost, narcotic use, and medication errors.

Analgesics↗