Biomedical subjects

Christopher Ng

Publications and source records attributed to Christopher Ng.

9 recordsLinked to original sources

PubMed2025

A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy.

The study of disease modifiers is a powerful way to identify patho-mechanisms associated with disease. Using the strong genetic traits of Huntington's disease (HD), we identified a rare, single-nucleotide polymorphism (SNP) in WDFY3 associated with a delayed age of onset of up to 23 years. Remarkably, the introduction of the orthologous SNP into mice recapitulates this neuroprotection, significantly delaying neuropathological and behavioral dysfunction in two models of HD. The SNP increases expression of the protein autophagy-linked Fab1, YOTB, Vac1, and EEA1 (FYVE) protein (Alfy), an autophagy adaptor protein for the clearance of aggregated proteins, whose ectopic overexpression is sufficient to capture the neuroprotective effects of the variant. Increasing Alfy expression protects not only against HD but also against the toxicity due to phospho-α-synuclein and AT8-positive accumulation. By combining human and mouse genetics, we have uncovered a pathway that protects against multiple proteinopathies, revealing a much-sought-after, shared therapeutic target across a broad range of neurodegenerative diseases.

Animals↗

PubMed2005

Seroprevalence of Helicobacter pylori in New York City populations originating in East Asia.

Helicobacter pylori prevalence is higher in developing countries than in industrialized countries, and within the latter, higher among immigrants than among nativeborn residents. Using a point-prevalence survey, we sought to identify risk factors for H. pylori seropositivity in US urban East Asian-born populations. At a clinic in New York City, we consecutively enrolled 194 East Asian-born adults, who then responded to a survey and provided a blood sample. Assays were performed to detect IgG antibodies against whole cell (WC) and cytotoxin associated gene A (CagA) antigens of H. pylori. For this group (mean age 50.2+/-14.7 years), the mean period of residence in the United States was 11.9+/-7.7 years. The total H. pylori seroprevalence was 70.1%, with highest (81.4%) in Fujianese immigrants. Multiple logistic regression analysis indicated an independent association of H. pylori seropositivity with Fujianese origin [odds ratios (OR) =2.3, 95% confidence interval (95% CI) =1.05-5.0] and inverse associations with period in the United States (OR per year of residency in the United States =0.95, 95% CI =0.91-0.99) and with a history of dyspepsia (OR for a history of stomach pain =0.52, 95% CI =0.3-1.0). We conclude that H. pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies.

Adult↗

PubMed2005

Prospective randomized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy.

PURPOSE: We report on a prospective randomized comparison of transperitoneal versus retroperitoneal laparoscopic radical nephrectomy for renal tumor. MATERIALS AND METHODS: Between June 1999 and June 2001, 102 consecutive eligible patients with a computerized tomography identified renal tumor were prospectively randomized to undergo either a transperitoneal (group 1, 50 patients) or retroperitoneal (group 2, 52 patients) laparoscopic radical nephrectomy with intact specimen extraction. Exclusion criteria for the study included body mass index greater than 35 or a history of prior major abdominal surgery in the quadrant of interest. Both groups were matched regarding age (63 versus 65 years, p = 0.69), BMI (29 versus 28, p = 0.89), American Society of Anesthesiologists class (2.7 versus 2.8, p = 0.37), laterality (right side 46% versus 48%, p = 0.85) and mean tumor size (5.3 versus 5.0 cm, p = 0.73). RESULTS: All 102 procedures were technically successful without the need for open conversion. Compared to the transperitoneal approach, the retroperitoneal approach was associated with a shorter time to renal artery control (91 versus 34 minutes, p <0.0001), shorter time to renal vein control (98 versus 45 minutes, p <0.0001) and shorter total operative time (207 versus 150 minutes, p = 0.001). However, the transperitoneal and retroperitoneal approaches were similar in terms of estimated blood loss (180 versus 242 cc, p = 0.13), hospital stay (43 versus 45 hours, p = 0.55), intraoperative complications (10% versus 7.7%, p = 0.30), postoperative complications (20% versus 13.5%, p = 0.14) and postoperative analgesia requirements (27 versus 26 mg MSO4 equivalent p = 0.13). Pathology revealed renal cell carcinoma in 84% and 75% of cases, respectively, with no positive surgical margin in any case. CONCLUSIONS: Laparoscopic radical nephrectomy can be performed efficiently and effectively with the transperitoneal or the retroperitoneal approach. While renal hilar control and total operative time may be quicker with retroperitoneoscopy, the approaches are similar in terms of other patient outcomes evaluated.

Adult↗

PubMed2004

Degradation of NF-kappa B in T cells by gangliosides expressed on renal cell carcinomas.

T cells from cancer patients are often functionally impaired, which imposes a barrier to effective immunotherapy. Most pronounced are the alterations characterizing tumor-infiltrating T cells, which in renal cell carcinomas includes defective NF-kappaB activation and a heightened sensitivity to apoptosis. Coculture experiments revealed that renal tumor cell lines induced a time-dependent decrease in RelA(p65) and p50 protein levels within both Jurkat T cells and peripheral blood T lymphocytes that coincided with the onset of apoptosis. The degradation of RelA/p50 is critical for SK-RC-45-induced apoptosis because overexpression of RelA in Jurkat cells protects against cell death. The loss of RelA/p50 coincided with a decrease in expression of the NF-kappaB regulated antiapoptotic protein Bcl-xL at both the protein and mRNA level. The disappearance of RelA/p50 protein was mediated by a caspase-dependent pathway because pretreatment of T lymphocytes with a pan caspase inhibitor before coculture with SK-RC-45 blocked RelA and p50 degradation. SK-RC-45 gangliosides appear to mediate this degradative pathway, as blocking ganglioside synthesis in SK-RC-45 cells with the glucosylceramide synthase inhibitor, PPPP, protected T cells from tumor cell-induced RelA degradation and apoptosis. The ability of the Bcl-2 transgene to protect Jurkat cells from RelA degradation, caspase activation, and apoptosis implicates the mitochondria in these SK-RC-45 ganglioside-mediated effects.

Adjuvants, Immunologic↗

PubMed2004

Laparoscopic nephron-sparing surgery for two or more ipsilateral renal tumors.

OBJECTIVES: To review our experience with laparoscopic nephron-sparing surgery in the management of two or more synchronous, ipsilateral renal masses. Minimally invasive nephron-sparing procedures are increasingly used for the treatment of select patients with a single, small renal tumor. METHODS: Since 1998, we have performed laparoscopic nephron-sparing surgery in 288 consecutive patients, including laparoscopic partial nephrectomy (n = 200) and renal cryotherapy (n = 88). Of these, 13 patients (4.5%) were treated for synchronous ipsilateral renal masses. RESULTS: A total of 27 renal tumors were treated in 13 patients. The patients were divided into four groups on the basis of the treatment. Group 1 (n = 3) underwent en-bloc laparoscopic partial nephrectomy encompassing both tumors; group 2 (n = 2) underwent individual laparoscopic partial nephrectomy of discrete masses during the same procedure; group 3 (n = 2) had one mass treated with partial nephrectomy and the other mass treated with cryotherapy; and group 4 (n = 6) had all tumors treated with cryotherapy. All cases were completed successfully without conversion to open surgery or laparoscopic nephrectomy. The mean overall operative time was 4.3 hours, and the mean blood loss was 169 mL. No intraoperative complications occurred. Three patients had postoperative complications, none requiring re-exploration. One patient in group 4 developed de novo tumors in the treated kidney, located distant from the cryoablated sites. CONCLUSIONS: Laparoscopic partial nephrectomy is an emerging, efficacious laparoscopic treatment option for select patients. Laparoscopic cryotherapy is a useful alternative or adjunct to partial nephrectomy. The judicious combination of these complementary techniques further extends the scope of minimally invasive nephron-sparing surgery.

Angiomyolipoma↗

PubMed2004

Laparoscopic ureterocalicostomy: initial experience.

PURPOSE: Ureterocalicostomy is a reconstructive option in the rare patient with surgically failed or difficult ureteropelvic junction (UPJ) obstruction with fibrosis and significant hydronephrosis. We introduce the technique of laparoscopic ureterocalicostomy. MATERIALS AND METHODS: Laparoscopic ureterocalicostomy was performed in 2 patients, of whom 1 had UPJ obstruction and multiple secondary calculi in a dilated, dependent lower pole calix, and 1 had surgically failed UPJ obstruction with a scarred pelvis and significant hydronephrosis. Using a transperitoneal technique the UPJ was dismembered and suture ligated, the cut end of the ureter was spatulated, the attenuated lower pole renal parenchyma was amputated and mucosa-to-mucosa ureterocaliceal anastomosis was performed with running 4-zero absorbable suture over a stent. In the first case 32 renal calculi were also removed using a combination of laparoscopic nephroscopy and intraoperative ultrasonography. RESULTS: In cases 1 and 2 operative time was 5.2 and 2.5 hours, estimated blood loss was 200 and 75 cc, and hospital stay was 2 days, respectively. There were no intraoperative complications. The stent was removed at 8 and 5 weeks, respectively. Postoperative retrograde pyelogram and diuretic renal scan confirmed anastomotic patency and improved drainage in each patient. At 9 months patient 1 remains without flank symptoms and a second renal scan at 6 months showed further improvement in drainage. Patient 2, who continued to be symptomatic with flank discomfort despite objective improvement in drainage parameters, elected secondary nephrectomy at 6 months. CONCLUSIONS: Laparoscopic ureterocalicostomy is feasible and it effectively duplicates established open surgical principles. To our knowledge the initial experience in the literature is presented.

Adult↗

PubMed2003

Laparoscopic upper pole partial nephrectomy with concomitant en bloc adrenalectomy.

OBJECTIVES: To report our experience with laparoscopic partial nephrectomy for renal tumor with concomitant adrenalectomy. An upper pole renal tumor may contiguously involve the adrenal gland, requiring concomitant adrenalectomy. Although commonly performed in the setting of laparoscopic radical nephrectomy, concomitant adrenalectomy has not been described during laparoscopic partial nephrectomy. METHODS: Four patients with an upper pole renal tumor and suspected adrenal involvement underwent laparoscopic partial nephrectomy with concomitant ipsilateral adrenalectomy. Preoperative three-dimensional computed tomography revealed the renal tumor to be closely abutting the adrenal gland in 3 patients and a 4-cm adrenal mass in 1 patient. The mean renal tumor size was 3.2 cm (range 1.4 to 6.6). To maintain oncologic principles, our transperitoneal laparoscopic technique excises the adrenal gland en bloc with the renal tumor. As such, adrenalectomy is performed first, followed by partial nephrectomy, incorporating hilar control, tumor excision, and sutured renal reconstruction. RESULTS: All four procedures were performed without open conversion or intraoperative complications. The mean renal warm ischemia time was 36 minutes, estimated blood loss 169 mL, total operating time 3.9 hours, and hospital stay 3.2 days. One patient developed a transient urinary leak postoperatively. Pathologic examination of the renal tumor revealed renal cell carcinoma (n = 1), dystrophic calcification with ectopic bone formation (n = 1), adult mesoblastic nephroma (n = 1), and subcapsular heterotopic adrenal cortex with cyst (n = 1), all with negative surgical margins. Pathologic examination of the adrenal gland revealed adenoma in 1 case and a normal adrenal gland without malignant involvement in 3 cases. All patients were disease free at last follow-up (mean 6.2 months, range 2 to 12). CONCLUSIONS: In patients with an upper pole renal tumor and radiologically suspected adrenal involvement, laparoscopic partial nephrectomy with concomitant adrenalectomy can be performed efficaciously respecting oncologic principles.

Adenoma↗

PubMed2003

Laparoscopic ice slush renal hypothermia for partial nephrectomy: the initial experience.

PURPOSE: We describe a novel technique of laparoscopic renal hypothermia with intracorporeal ice slush during partial nephrectomy as well as clinical experience with the initial 12 patients. MATERIALS AND METHODS: A total of 12 select patients with an infiltrating renal tumor who were candidates for nephron sparing surgery underwent transperitoneal laparoscopic partial nephrectomy with renal hypothermia. An Endocatch II (United States Surgical Corp., Norwalk, Connecticut) bag was placed around the mobilized kidney and its drawstring was cinched around the intact renal hilum. The renal artery and vein were occluded en bloc with a Satinsky clamp. The bottom of the engaged bag was retrieved through a 12 mm port site and opened, and ice slush was introduced within the bag to completely surround the kidney. After renal hypothermia was achieved laparoscopic partial nephrectomy was performed by duplicating open surgical techniques. Renal parenchymal temperature was measured using a thermocouple needle in 5 patients. Median tumor size was 3.2 cm (range 1.5 to 5.5), 6 tumors (50%) were central in location and an imperative indication for partial nephrectomy was present in 7 patients (58%). RESULTS: All procedures were successfully completed laparoscopically without open conversion. Median time to deploy the bag around the kidney was 7 minutes (range 5 to 20), the median volume of ice slush introduced was 600 cc (range 300 to 750) and the time needed to insert the ice slush was 4 minutes (range 3 to 10). Median blood loss was 200 cc, total ischemia time was 43.5 minutes (range 25 to 55) and total operative time was 4.3 hours (range 3 to 5.5). Nadir renal parenchymal temperature was 5C to 19C and the mean decrease in systemic temperature was 0.6C. Histopathology confirmed renal cell carcinoma in 11 patients (92%), of whom all had negative surgical margins. Intraoperative complications occurred in 2 initial patients, including partial bag slippage in 1 and Satinsky clamp malfunction in 1. Postoperatively renal scan confirmed a functioning ipsilateral kidney in all cases. CONCLUSIONS: To our knowledge we present the initial clinical report of laparoscopic renal hypothermia for partial nephrectomy. By replicating standard open surgical practice our intracorporeal ice slush technique has the potential to extend the scope of laparoscopic partial nephrectomy to more complicated renal tumors.

Adult↗

PubMed2002

The impact of cystinuria on renal function.

PURPOSE: Patients with cystinuria frequently have recurrent renal calculi and may subsequently require multiple stone removing procedures during their lifetime which could have an impact on overall renal function. We determined the potential impact of cystinuria and cystine stone formation on the level of renal function compared to calcium oxalate stone formers. MATERIALS AND METHODS: Clinical data on 40 cystinuric patients followed at 2 medical centers and 45 such individuals in a large stone population data base were analyzed. These results were compared to data on 3,964 calcium oxalate stone formers enrolled in this data base. RESULTS: Mean serum creatinine plus or minus standard deviation for stone forming cystinuric patients was significantly higher than that of the calcium oxalate cohort (1.13 +/- 0.28 versus 1.01 +/- 0.28 mg./100 ml., p = 0.0001). A significantly greater percentage of cystinuric patients (5.8%) had an abnormally increased serum creatinine compared to the calcium oxalate stone formers (2.2%, p = 0.046). Male gender, increasing number of open surgical stone removing procedures and nephrectomy were significant variables associated with an increased serum creatinine (p = 0.0010, p = 0.0038, p = 0.0133, respectively). An increasing number of open surgical stone removing procedures had a significant positive correlation with performance of nephrectomy in the cystinuric population (p = 0.0166). A significantly greater percentage of cystinuric patients compared to the calcium oxalate cohort were subjected to nephrectomy (14.1% versus 2.9%, p = 0.007). CONCLUSIONS: Cystinuric patients have higher serum creatinine levels than calcium oxalate stone formers and they are at more risk for renal loss. When stone removal is required, a minimally invasive approach is preferred.

Adolescent↗