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Jennifer Smith

Publications and source records attributed to Jennifer Smith.

At least 19 recordsLinked to original sources

Comparison of clinical outcomes of robotic versus open pyeloplasty in infants under 6 months.

INTRODUCTION: Robotic pyeloplasties have become the popular approach for surgical repair of ureteropelvic junction obstruction (UPJO) in the pediatric population. In infants less than 6 months old, there is concern for lack of intra-abdominal working space and lack of benefit compared to an open approach. Our aim was to compare the peri-operative and post-operative outcomes of patients undergoing open versus robotic pyeloplasty under six months of age. METHODS: A retrospective review was performed of patients less than six months of age undergoing robotic or open pyeloplasty between 2020 and 2024 at a single institution. Patient demographics and clinical outcomes were collected and compared. Surgical success was defined as a >50% reduction in the antero-pelvic diameter (APD) of the affected kidney at one year post pyeloplasty. RESULTS: A total of 32 patients were identified (16 robotic and 16 open), median age at surgery was 4 months old. There was no significant difference in length of hospital stay or narcotic usage between the two groups. The robotic cohort had a significantly longer operative time (209.5 min vs 142.5 min, p < 0.001) compared to the open cohort. There was no significant difference between post-operative complication or surgical success rates between the two groups. CONCLUSION: In this small series, robotic and open pyeloplasty both remain viable options for infants less than 6 months of age with equivalent surgical outcomes and lengths of hospital stay.

Humans↗

Characterizing the genetic diversity and population structure of Plasmodium knowlesi in Aceh Province, Indonesia.

As in other parts of Southeast Asia, efforts to achieve or sustain malaria elimination in Indonesia have been threatened by the emergence of human infection with the primate species P. knowlesi. To understand the transmission dynamics of this species, investigation of P. knowlesi genetic diversity and population structure is needed. A molecular surveillance study was conducted in two phases between June 2014 and September 2018 at five primary health facilities in Aceh Province, Indonesia, an area nearing malaria elimination. Dried blood spot samples were collected from patients presenting with suspected malaria and testing positive for malaria by microscopy. PCR was performed for molecular confirmation and species identification. Forty-six samples were confirmed to be P. knowlesi, of which 41 were amplified with genotyping targeting ten known P. knowlesi microsatellite markers. For samples within a site, nearly all (9 of 10 loci) or all loci were polymorphic. Across sites, multiple identical haplotypes were observed, though linkage distribution in the population was low (index of association (IAS)&#x2009;=&#x2009;0.008). The parasite population was indicative of low diversity (expected heterozygosity [HE] =&#x2009; 0.63) and low complexity demonstrated by 92.7% monoclonal infections, a mean multiplicity of infection of 1.06, and a mean within-host infection fixation index (FST) of 0.05. Principal coordinate and neighbour-joining tree analyses indicated that P. knowlesi strains from Aceh were distinct from those reported in Malaysia. In a near-elimination setting in Indonesia, we demonstrate the first evidence that P. knowlesi strains were minimally diverse and were genetically distinct from Malaysian strains, suggesting highly localized transmission and limited connectivity to Malaysia. Ongoing genetic surveillance of P. knowlesi in Indonesia can inform tracking and planning of malaria control and elimination efforts.

Plasmodium knowlesi↗

Copy number polymorphism in Fcgr3 predisposes to glomerulonephritis in rats and humans.

Identification of the genes underlying complex phenotypes and the definition of the evolutionary forces that have shaped eukaryotic genomes are among the current challenges in molecular genetics. Variation in gene copy number is increasingly recognized as a source of inter-individual differences in genome sequence and has been proposed as a driving force for genome evolution and phenotypic variation. Here we show that copy number variation of the orthologous rat and human Fcgr3 genes is a determinant of susceptibility to immunologically mediated glomerulonephritis. Positional cloning identified loss of the newly described, rat-specific Fcgr3 paralogue, Fcgr3-related sequence (Fcgr3-rs), as a determinant of macrophage overactivity and glomerulonephritis in Wistar Kyoto rats. In humans, low copy number of FCGR3B, an orthologue of rat Fcgr3, was associated with glomerulonephritis in the autoimmune disease systemic lupus erythematosus. The finding that gene copy number polymorphism predisposes to immunologically mediated renal disease in two mammalian species provides direct evidence for the importance of genome plasticity in the evolution of genetically complex phenotypes, including susceptibility to common human disease.

Animals↗

Rapid growth of Merkel cell carcinoma after treatment with rituximab.

Merkel cell carcinoma is an uncommon neuroendocrine carcinoma of the skin. We report a case of rapid growth of Merkel cell carcinoma after treatment with rituximab, a new anti-CD20 monoclonal antibody, for acquired factor VIII inhibitor. We propose that rituximab may place patients at higher risk for aggressive Merkel cell carcinoma thus necessitating the need for increased long-term surveillance of these patients.

Aged↗

A case of an adverse reaction to topical 5-fluorouracil in irradiated skin.

A 73-year-old Caucasian male was treated in the dermatology clinic for squamous cell carcinoma (SCC) of the scalp by Mohs micrographic surgery. The patient subsequently received radiation therapy because of possible calvarium invasion. Approximately 2 years later, the patient developed Bowen's disease within the previously irradiated skin flap. The lesion was treated with topical 5-fluorouracil (5-FU) twice daily for 4 weeks, and subsequently developed a 2 x 2 cm full-thickness ulceration with exposed calvarium.

Administration, Cutaneous↗

Tools and strategies for physiological genomics: the Rat Genome Database.

The broad goal of physiological genomics research is to link genes to their functions using appropriate experimental and computational techniques. Modern genomics experiments enable the generation of vast quantities of data, and interpretation of this data requires the integration of information derived from many diverse sources. Computational biology and bioinformatics offer the ability to manage and channel this information torrent. The Rat Genome Database (RGD; http://rgd.mcw.edu) has developed computational tools and strategies specifically supporting the goal of linking genes to their functional roles in rat and, using comparative genomics, to human and mouse. We present an overview of the database with a focus on these unique computational tools and describe strategies for the use of these resources in the area of physiological genomics.

Animals↗

Angiotensin converting enzyme insertion/deletion polymorphisms in vasovagal syncope.

UNLABELLED: Recent studies suggest vasovagal syncope (VVS) has a significant heritable component (crude estimate sibling relative risk (lambda(s)): 1080) indicating that at least some forms of VVS may have a genetic cause. Here we present the first study examining a potential genetic abnormality in VVS. METHODS: DNA was collected from consecutive patients attending our unit with head up tilt confirmed VVS (n=165). One hundred and fourteen affected and unaffected first-degree relatives of those with a definitive diagnosis of VVS and positive family history also provided DNA. RESULTS: DNA from 165 VVS index cases was genotyped for the ACE insertion/deletion polymorphism. Mean+/-SD age of cases was 56+/-19 years (103 (62%) females). There was no significant difference in distribution of ACE insertion or deletion gene frequencies in cases compared with a large (>6000 subjects) national control population. No preferential transmission of alleles in families was identified using tests of association (P=0.1789) CONCLUSION: We have shown using both a case control and a small family based association study that polymorphisms of ACE alone are not associated with increased risk of VVS. Further studies are planned to clarify the genotype/phenotype relationship in VVS and examine other candidate genes.

Case-Control Studies↗

An implicit test of the associations between children and sex in pedophiles.

Pedophiles are motivated to disguise their thoughts and feelings about their sexual beliefs and attraction toward children. New developments using implicit measures of associations have been successful in accessing socially stigmatic beliefs, even in cases in which the participant is resistant to this disclosure. Using an implicit measure, the authors show that pedophiles have an association between children and sex, whereas nonpedophilic offenders have an association between adults and sex. The task can therefore identify a core cognitive abnormality that may underpin some pedophilic deviant sexual behavior.

Adult↗

Antibody blockade of TNF-alpha reduces inflammation and scarring in experimental crescentic glomerulonephritis.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine produced by macrophages, and by renal mesangial and tubular epithelial cells. It stimulates the release of interleukin (IL)-1beta, monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta (TGF-beta). Blockade of TNF-alpha is currently used clinically in several autoimmune inflammatory diseases. We hypothesised that blocking TNF-alpha with a monoclonal antibody would prevent inflammation and renal fibrosis in crescentic glomerulonephritis. METHODS: Nephrotoxic nephritis was induced in Wistar Kyoto (WKY) rats by intravenous injection of rabbit antirat glomerular basement membrane (GBM) nephrotoxic serum (NTS). Anti-TNF-alpha monoclonal antibody or saline was given intraperitoneally three times per week in four protocols: experiment 1, days 0 to 7; experiment 2, days 0 to 14 and days 4 to 14; experiment 3, days 4 to 28; and experiment 4, days 14 to 28. RESULTS: In experiment 1, rats treated from disease induction had less glomerular fibrinoid necrosis and fewer glomerular macrophages at day 7. In experiment 2, rats treated from day 0 or day 4 showed improved renal function, as judged by serum creatinine, with a significant reduction in crescents. In experiment 3, anti-TNF-alpha treatment significantly reduced urine protein to creatinine ratio and urinary MCP-1 levels. Serum creatinine was preserved at both day 14 and day 28. Tubulointerstitial inflammation, glomerular and tubulointerstitial scarring, and markers of fibrosis [alpha-smooth muscle actin (alpha-SMA) and type IV collagen] were significantly less in treated rats at day 28. In experiment 4, serum creatinine was higher and tubulointerstitial scarring was less in delayed-treated animals. CONCLUSION: Neutralization of endogenous TNF-alpha reduces glomerular inflammation, crescent formation, and tubulointerstitial scarring, with preservation of renal function, in experimental crescentic glomerulonephritis. TNF-alpha blockade is effective even when introduced at the time of maximum glomerular inflammation.

Animals↗

The emergence of mature gestural patterns in the production of voiceless and voiced word-final stops.

The organization of gestures was examined in children's and adults' samples of consonant-vowel-stop words differing in stop voicing. Children (5 and 7 years old) and adults produced words from five voiceless/voiced pairs, five times each in isolation and in sentences. Acoustic measurements were made of vocalic duration, and of the first and second formants at syllable center and voicing offset. The predicted acoustic correlates of syllable-final voicing were observed across speakers: vocalic segments were shorter and first formants were higher in words with voiceless, rather than voiced, final stops. In addition, the second formant was found to differ depending on the voicing of the final stop for all speakers. It was concluded that by 5 years of age children produce words ending in stops with the same overall gestural organization as adults. However, some age-related differences were observed for jaw gestures, and variability for all measures was greater for children than for adults. These results suggest that children are still refining their organization of articulatory gestures past the age of 7 years. Finally, context effects (isolation or sentence) showed that the acoustic correlates of syllable-final voicing are attenuated when words are produced in sentences, rather than in isolation.

Child↗

A novel combination of cisplatin, irinotecan, and capecitabine in patients with advanced cancer.

BACKGROUND: We conducted a dose escalation study combining cisplatin, irinotecan, and capecitabine (CIC), aiming to establish the maximum tolerated doses (MTD), side effect profile, and dose-limiting toxicity (DLT) of this novel regimen. PATIENTS AND METHODS: Intravenous cisplatin and irinotecan were to be administered on days 1 and 8, and oral capecitabine on days 1-14 of a 3-week cycle. The study was conducted in three parts. Part A: escalating doses of irinotecan (40 --> 80 mg/m2) and capecitabine (1000 --> 3300 mg/d) combined with a fixed dose of cisplatin (30 mg/m2). Part B: escalating doses of irinotecan (MTD-A --> MTD-A + 40 mg/m2) with fixed doses of cisplatin (20 mg/m2) and capecitabine (MTD-A level). Part C: escalating doses of capecitabine (1300 mg/d-->2600 mg/d) with fixed doses of cisplatin (20 mg/m2) and irinotecan (60 mg/m2). RESULTS: Of 51 eligible patients 27 (53%) were male, median age was 58 years and 88% had PS 0-1. Major primary disease sites were colorectal (24%), unknown (14%), stomach (14%), and pancreas (12%). MTD-A was cisplatin 30 mg/m2, irinotecan 60 mg/m2, capecitabine 1000 mg/d and MTD-B was cisplatin 20 mg/m2, irinotecan 90 mg/m2, capecitabine 1000 mg/d. An MTD was not formally established for part C. DLTs consisted of infection with neutropenia (1), diarrhea and fatigue (1), hypokalemia (1), diarrhea and febrile neutropenia (1) and C2 delay of > or = 2 weeks or 25% dose reduction in C1 due to neutropenia or thrombocytopenia (6). Seven patients had a partial response to treatment (four colorectal, one SCLC, one NSCLC, one unknown primary), twenty seven SD (53%), twelve PD (24%) and five NE (10%). CONCLUSION: CIC was associated with moderate toxicity and only modest antitumor activity. We conclude that this regimen has insufficient activity to justify further study in the phase II setting.

Adult↗