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Biomedical subjects

B D Hamilton

Publications and source records attributed to B D Hamilton.

At least 19 recordsLinked to original sources

Transperitoneal laparoscopic adrenalectomy.

Laparoscopic adrenalectomy has been demonstrated by many institutions to be a safe and effective approach to benign adrenal lesions. As surgical skills improve, it will most likely be comparable with open adrenalectomy in overall cost. Although it is technically demanding and takes slightly longer than open surgery, the benefits to the patient in terms of hospital stay, convalescence, and cosmetic results have been conclusively reported. The decision to use a transperitoneal or retroperitoneal access is mostly a function of surgeon preference, with similar outcomes by either approach. It is more important that the surgeon be comfortable with the selected approach. Laparoscopic adrenalectomy has become the gold standard for benign adrenal lesions.

Adrenalectomy↗

Urethral calculi managed with transurethral Holmium laser ablation.

In situ Holmium laser lithotripsy is a safe, effective procedure for the treatment of impacted urethral stones. This procedure can be performed transurethrally as an outpatient with minimal tissue trauma and render patients stone free. The authors utilized this procedure in 2 patients whose anatomy did not allow the calculi to be manipulated into the urinary bladder in a retrograde manner. Because of its successful use elsewhere in the urinary tract, we believe that Holmium laser lithotripsy may be the treatment of choice for impacted urethral stones.

Adolescent↗

Survey of neuromuscular injuries to the patient and surgeon during urologic laparoscopic surgery.

OBJECTIVES: Laparoscopy may be complicated by neuromuscular injuries, both to the patient and to the surgeon. We used a survey to estimate the incidence of these injuries during urologic laparoscopic surgery, to assess risk factors for these injuries, and to determine preventive measures. METHODS: A survey of neuromuscular injuries associated with laparoscopy submitted to 18 institutions in the United States was completed by 18 attending urologists from 15 institutions. RESULTS: From among a total of 1651 procedures, there were 46 neuromuscular injuries in 45 patients (2.7%), including abdominal wall neuralgia (14), extremity sensory deficit (12), extremity motor deficit (8), clinical rhabdomyolysis (6), shoulder contusion (4), and back spasm (2). Neuromuscular injuries were twice as common with upper retroperitoneal as with pelvic laparoscopy (3. 1% versus 1.5%). Among patients with neuromuscular injuries, those with rhabdomyolysis were heavier (means 91 versus 80 kg) and underwent longer procedures (means 379 versus 300 minutes), and those with motor deficits were older (means 51 versus 42 years of age). Of the surgeons, 28% and 17% reported frequent neck and shoulder pain, respectively. CONCLUSIONS: Although not common, neuromuscular injuries during laparoscopy do contribute to morbidity. Abdominal wall neuralgias, injuries to peripheral nerves, and joint or back injuries likely occur no more frequently than during open surgery, but risk of rhabdomyolysis may be increased. Positioning in a partial rather than full flank position may reduce the incidence of some injuries. Measures to reduce neuromuscular strain on the surgeon during laparoscopy should be considered.

Abdominal Muscles↗

Comparison of laparoscopic versus open nephrectomy in the pediatric population.

PURPOSE: Laparoscopic renal surgery has become an accepted approach for benign disease in adults. We compare our experience with laparoscopic and open nephrectomy in a pediatric population. MATERIALS AND METHODS: A total of 10 pediatric patients underwent laparoscopic nephrectomy or nephroureterectomy and an additional 10 consecutive children underwent similar open procedures. All patients had benign disease and were treated at a single institution. Medical records were reviewed retrospectively for relevant clinical data. RESULTS: Planned surgery was completed in all cases. There were no conversions to open surgery in the laparoscopic group. Mean operative time was 175.6 versus 120.2 minutes (p = 0.01) and mean hospital stay was 22.5 versus 41.3 hours (p = 0.03) in the laparoscopic and open nephrectomy groups, respectively. Blood loss was not statistically different. Analgesic use was qualitatively less in the laparoscopic nephrectomy group. CONCLUSIONS: Laparoscopic nephrectomy and nephroureterectomy may be performed safely in children. While operative time was somewhat longer in our initial laparoscopic series, postoperative hospital stay was significantly shorter than for open surgery. Further experience with this technique is warranted.

Child↗

Ammonium acid urate calculi: a reevaluation of risk factors.

PURPOSE: We reevaluate the demographic and metabolic risk factors for ammonium acid urate stones. MATERIALS AND METHODS: Since 1986, 23 women and 21 men ranging in age from 20 to 81 years (mean 48.7) were treated for stones partly composed of ammonium acid urate. Stone composition ranged from 2 to 60% ammonium acid urate (mean 24.1) of the total stone mass. No patient had a pure ammonium acid urate stone, although 11 (25%) had stones with ammonium acid urate as the predominant crystal. RESULTS: In the 44 patients 1 or more potential risk factors for ammonium acid urate were identified. Of the patients 11 (25%) had a history of inflammatory bowel disease with 10 (22.7%) having undergone ileostomy diversion, 6 (13.6%) admitted to a history of significant laxative use or abuse, 18 (40.9%) were morbidly obese, 16 (36.4%) had a history of recurrent urinary tract infections and 9 (20.5%) had a history of recurrent uric acid stones. CONCLUSIONS: Patients clearly at risk for stones with an ammonium acid urate component include those with a history of inflammatory bowel disease and ileostomy diversion or laxative abuse. Other factors that may potentially enhance ammonium acid urate stone formation include morbid obesity, recurrent uric acid calculi and recurrent urinary tract infection. A careful history followed by further metabolic evaluation is warranted in these patients.

Adult↗

Percutaneous endoscopic trigonoplasty in children: long-term outcomes and modifications in technique.

PURPOSE: Long-term outcomes of a minimally invasive method of correcting vesicoureteral reflux are presented with a discussion of the modification in our original technique. PATIENTS AND METHODS: A total of 29 children (46 refluxing ureters), 14 months to 18 years old, underwent percutaneous endoscopic trigonoplasty (PET) between December 1994 and June 1996. Follow-up ranged from 19 to 37 months. Reflux was grade 1 in 2, grade 2 in 16, grade 3 in 19, grade 4 in 8, and grade 5 in 1. The technique was a Gil-Vernet method in the first 23 patients and Cohen reimplantation in the last 6 patients. RESULTS: Resolution of reflux was observed to decrease from 63% to 47% with long-term (30-37 months') follow-up using the Gil-Vernet technique. Resolution was greater with unilateral reflux than bilateral reflux (83% v. 27%, respectively). The Cohen technique resulted in resolution of reflux in 83%; however, the operating time nearly doubled when compared with the Gil-Vernet group. In both groups, failure was unrelated to grade of reflux, age, operative sequence, or bladder instability. CONCLUSIONS: Although showing an improvement in resolution of reflux over the Gil-Vernet PET procedure, the Cohen PET reimplant has a lower success rate than traditional open operative reimplants. The PET also requires more operating time and two operating surgeons. Despite some advantages in the promptness of recovery, we do not recommend PET by either technique at this time. Future modifications may make this approach more tenable.

Adolescent↗

Interaction of Mycobacterium tuberculosis-induced transforming growth factor beta1 and interleukin-10.

Mycobacterium tuberculosis is associated with the activation of cytokine circuits both at sites of active tuberculosis in vivo and in cultures of mononuclear cells stimulated by M. tuberculosis or its components in vitro. Interactive stimulatory and/or inhibitory pathways are established between cytokines, which may result in potentiation or attenuation of the effects of each molecule on T-cell responses. Here we examined the interaction of transforming growth factor beta1 (TGF-beta1) and interleukin-10 (IL-10) in purified protein derivative (PPD)-stimulated human mononuclear cell cultures in vitro. TGF-beta1 induced monocyte IL-10 (but not tumor necrosis factor alpha) production (by 70-fold, P < 0.02) and mRNA expression in the absence but not in the presence of PPD. Both exogenous recombinant (r) IL-10 and rTGF-beta1 independently suppressed the production of PPD-induced gamma interferon (IFN-gamma) in mononuclear cells from PPD skin test-positive individuals. Synergistic suppression of IFN-gamma in cultures containing both rTGF-beta1 and rIL-10 was only seen when the responder cell population were peripheral blood mononuclear cells (PBMC) and not monocyte-depleted mononuclear cells and when PBMC were pretreated with rTGF-beta1 but not with rIL-10. Suppression of PPD-induced IFN-gamma in PBMC containing both rTGF-beta1 (1 ng/ml) and rIL-10 (100 pg/ml) was 1.5-fold higher (P < 0.05) than cultures containing TGF-beta1 alone and 5.7-fold higher (P < 0.004) than cultures containing IL-10 alone. Also, neutralization of endogenous TGF-beta1 and IL-10 together enhanced PPD-induced IFN-gamma in PBMC in a synergistic manner. Thus, TGF-beta1 and IL-10 together potentiate the downmodulatory effect on M. tuberculosis-induced T-cell production of IFN-gamma, and TGF-beta1 alone enhances IL-10 production. At sites of active M. tuberculosis infection, these interactions may be conducive to the suppression of mononuclear cell functions.

Animals↗

Laparoscopic adrenalectomy: the preferred choice? A comparison to open adrenalectomy.

PURPOSE: We compare the effectiveness and efficiency of laparoscopic adrenalectomy to open surgical management of adrenal disorders. MATERIALS AND METHODS: A retrospective comparison was undertaken of 21 patients who underwent transperitoneal laparoscopic adrenalectomy between April 1996 and May 1997 with 17 patients who underwent open adrenalectomy between October 1994 and January 1996. Any patient suspected of having primary adrenal carcinoma and/or an adrenal lesion larger than 6 cm. was excluded from the study. RESULTS: Patient demographics were matched well. Mean laparoscopic surgical time was 79 minutes longer than for open surgery. After overcoming the learning curve, the surgical time decreased by 59 minutes in the last 10 laparoscopic adrenalectomies. All laparoscopic intraoperative complications were managed without the need for open surgical conversion. Postoperative characteristics demonstrated significant benefits in the laparoscopic group (p=0.001) with respect to days to return to full diet (1.7 versus 4.6), analgesic pain requirements and days of hospitalization (2.7 versus 6.2). CONCLUSIONS: Laparoscopic adrenalectomy offers significant postoperative benefits to patients with benign adrenal disease requiring surgical intervention. The surgical time is longer than that for open adrenalectomy but there was an encouraging reduction in time after overcoming the laparoscopic learning curve. Laparoscopic adrenalectomy is an excellent choice for tumors smaller than 6 cm. Its role for larger lesions and/or primary adrenal carcinoma is currently under investigation.

Adrenal Gland Neoplasms↗

Increased intra-abdominal pressure during pneumoperitoneum stimulates endothelin release in a canine model.

Prolonged pneumoperitoneum during laparoscopic surgery has been associated with oliguria in clinical experimental studies. Although the pathophysiology of this oliguria is thought to be renal parenchymal and venous compression, the role of the potent vasoconstrictor endothelin (ET) has not been studied. The purpose of this study was to investigate the effect of pneumoperitoneum on endothelin release and renal function in a canine model. Two groups of dogs were studied during pneumoperitoneum (Group 1, N = 7) or isolated left renal vein compression (Group 2, N = 6). Urine and plasma samples were collected for urine output, glomerular filtration rate (GFR), urine sodium, and plasma endothelin measurements. In Group 1, GFR fell significantly (p < 0.05) by 49% from a control of 0.88 +/- 0.12 mL/min per gram of kidney weight. Urine volume fell by 79% (p < 0.05) from a control value of 0.014 +/- 0.003 mL/min/gkw. Sodium excretion was decreased by 88%. Sodium reabsorption was significantly enhanced during pneumoperitoneum (99.56 +/- 0.15% v 98.44 +/- 0.25%). Arterial plasma ET concentrations were elevated by 8% during the first 20 minutes of pneumoperitoneum (30.8 +/- 3.6 v 33.3 +/- 3.4 pg/mL; p < 0.05). In Group 2, left renal vein compression resulted in a 31% decrease (p < 0.05) in GFR in the left kidney and a 25% decrease in the right kidney. Urine volume fell by 67% in the left kidney and 40% in the right. Renal venous ET concentrations also increased after renal vein compression. Although the mechanism by which oliguria occurs during pneumoperitoneum is not fully understood, the ET concentration was elevated. Because ET can decrease RBF, GFR, and sodium excretion, it may contribute to the oliguria observed during long periods of pneumoperitoneum.

Abdomen↗

Apparent unilateral ureteropelvic junction obstruction in the newborn: expectations for resolution.

PURPOSE: We retrospectively reviewed the records of patients with prenatal hydronephrosis to characterize those in whom it was more likely to resolve with conservative management. MATERIALS AND METHODS: We studied 51 patients in a 4-year period who presented with nonspecific unilateral hydronephrosis diagnosed by prenatal and confirmed by postnatal sonography. Patients were followed with sequential nuclear renograms with furosemide washout to evaluate function and drainage. In all cases a nonoperative approach was attempted. Pyeloplasty was performed only for poor or decreasing kidney function and/or drainage. RESULTS: Four of the 51 patients were lost to followup, 21 of the remaining 47 (45%) eventually underwent surgery, and 26 (55%) had complete normalization of renal function and washout pattern without surgery. There was no statistically significant correlation between hydronephrosis grade on initial postnatal sonography and the likelihood of nonsurgical resolution. However, the shape of the washout curve on nuclear renography was informative for predicting outcome, since 86% of the cases with a nonobstructive drainage pattern normalized without surgery, while 62% with indeterminate and only 18% with obstructive curves resolved with conservative management (p <0.01). Notably in 83% of the cases of normalization without surgery resolution occurred before age 18 months. Also, an initial obstructed washout pattern was more likely to be associated with a poor outcome. Of the 6 patients with less than 40% final differential function 5 had an obstructed washout pattern on the initial nuclear renogram. CONCLUSIONS: Patients diagnosed by prenatal ultrasound with apparent unilateral ureteropelvic junction obstruction generally do well with conservative treatment. However, those who present with an obstructed washout pattern are less likely to have resolution without surgery and more likely to have poor final differential function.

Female↗

Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis.

Blood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients. The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes.

DNA-Binding Proteins↗

Suppression of TNF-alpha gene expression by hemin: implications for the role of iron homeostasis in host inflammatory responses.

Tumor necrosis factor alpha (TNF-alpha) has multiple effects on iron homeostasis and erythropoiesis and has been implicated in the pathogenesis of the anemia of inflammation. We postulated that intracellular iron in turn may regulate the expression of TNF-alpha. In the human monocytic leukemia cell line, THP-1, low basal TNF-alpha message levels were stimulated (sevenfold) when serum was excluded from the culture medium. Addition of hemin completely suppressed TNF-alpha expression. Similarly, hemin suppressed lipopolysaccharide-induced expression of TNF-alpha. Sn-protoporphyrin, an inhibitor of heme oxygenase (which releases iron from hemin), prevented hemin-induced suppression of TNF-alpha expression. Conversely, the intracellular iron chelator, desferrioxamine, stimulated TNF-alpha expression. Thus, the expression of TNF-alpha, itself a physiological regulator of iron homeostasis, appears to be controlled by intracellular levels of iron.

Blood↗

Technique of laparoscopic adrenalectomy.

Laparoscopic adrenalectomy by the transperitoneal route has been shown to be a safe and effective approach to select adrenal pathology. Although the specific indications will continue to be refined, it is clear that for adrenal masses of 6 cm or less, laparoscopy provides excellent access with little additional risk to the patient. In addition there appears to be an improved postoperative course when compared with open adrenalectomy. This latter point, however, requires careful prospective studies to confirm this impression objectively. The operative times are longer by the laparoscopic approach, but undoubtedly these times will decrease with increasing experience and improved laparoscopic instrumentation.

Adrenalectomy↗

Mycobacterium tuberculosis (MTB)-stimulated production of nitric oxide by human alveolar macrophages and relationship of nitric oxide production to growth inhibition of MTB.

SETTING: Although nitric oxide (NO) is a major proximate mediator of microbicidal activity in murine macrophages against intracellular pathogens including mycobacteria, its production by and effector role in human macrophages is not clear. OBJECTIVE: To determine the capacity of Mycobacterium tuberculosis (MTB) to stimulate NO in human monocytes (MN) and alveolar macrophages (AM) and to assess the relationship between NO production and intracellular growth of MTB. DESIGN: NO production (measured as nitrite) by MTB (H37Ra)-infected macrophages and intracellular growth of MTB were measured in cells from 17 healthy subjects. RESULTS: MTB (5:1, MTB:cells) stimulated little to no NO by MN, but induced NO in AM at days 4 and 7 after infection. There was, however, variability in the response by AM to MTB: among seven subjects MTB-induced NO was low (4 +/- 2 microM, mean +/- SE); six subjects were moderate (56 +/- 11); four subjects were high (502 +/- 167). NO synthase inhibitors inhibited the production of NO by AM but did not significantly affect the intracellular growth of MTB, although a trend towards increased intracellular growth was seen on day 4 of culture. Intracellular growth of MTB in AM from low NO producers was significantly higher than that in AM from moderate NO producers, P < or = 0.05. Inducible NO synthase (iNOS) mRNA by RT-PCR was constitutively expressed by both MN and AM, but was further stimulated by MTB in AM > MN; MTB-induced iNOS protein was present in both MN and AM by Western blot analysis. CONCLUSION: Thus, MTB-infected human AM are capable of producing NO and NO production correlates with intracellular growth inhibition of MTB in AM suggesting that NO may serve either directly or indirectly as a mycobactericidal mediator in human tissue macrophages.

Adult↗

Modulation of IL-12 by transforming growth factor-beta (TGF-beta) in Mycobacterium tuberculosis-infected mononuclear phagocytes and in patients with active tuberculosis.

In humans, tuberculosis is associated with suppression of T-cell responses to antigens of Mycobacterium tuberculosis. Recently, the macrophage product, transforming growth factor-beta (TGF-beta) has been implicated in suppression of T-cell proliferation and cytokine production during tuberculosis. We studied the effect of TGF-beta on production of IL-12, and on the augmentation of M. tuberculosis-induced IFN gamma production by IL-12, in patients with pulmonary tuberculosis and by M. tuberculosis. Induction of IL-12 p35, but not IL-12 p40, by M. tuberculosis in monocytes was dependent on prior priming of the cells with IFN gamma. Expression of both IL-12 p40 and p35, however, was suppressed by TGF-beta. Further, TGF-beta interfered with the bioactivity of IL-12 in the enhancement of M. tuberculosis-induced IFN gamma mRNA expression and cytokine production. However, in mononuclear cells from patients with tuberculosis the main effect of TGF-beta on IL-12 appeared to be counter action to IL-12 induced IFN gamma production in response to M. tuberculosis.

Gene Expression Regulation↗

Decreased production of TGF-beta 1 by human alveolar macrophages compared with blood monocytes.

As the main immunocytes lining pulmonary alveoli, alveolar macrophages (AM) are critical to the maintenance of immune hemostasis of the lung. This study examined the capacity of AM obtained from healthy individuals in comparison with autologous blood monocytes (MN) to produce transforming growth factor-beta 1 (TGF-beta), a pivotal molecule in regulation of immune responses and in promotion of fibrosis. AM produced negligible TGF-beta in response to LPS at both 24 and 72 h of culture. In contrast, LPS induced significant levels of TGF-beta in MN cultures (79.5 +/- 35 pg/ml in AM vs 890 +/- 162 pg/ml in MN, p less than 0.001, at 24 h). AM also produced significantly less TGF-beta than MN in response to phorbol ester and Con A. By northern blot analysis, constitutive expression of TGF-beta mRNA was lower in AM than MN at the time of isolation and after 24 h of culture. Lower expression of steady state TGF-beta message was not due to a more rapid decay of its mRNA in AM. Furthermore, TGF-beta mRNA expression was up-regulated by rTGF-beta in MN but was not induced in AM. In contrast to TGF-beta, LPS-stimulated AM produced sixfold higher levels of TGF-alpha at 24 h than MN (p less than 0.01). Production of IL-10 by LPS-stimulated AM was sixfold lower than MN (p less than 0.005) at 24 h of culture, but was comparable with MN at 72 h. Both 10-day cultured monocytes and peritoneal macrophages also had reduced capacity to produce TGF-beta. Therefore, the inability to produce TGF-beta may be a feature of more differentiated mononuclear phagocytes. In health, the reduced expression of TGF-beta by AM and the intact ability to produce TGF-alpha and IL-10 may favor a timely and regulated host response to inhaled pathogens while limiting potentially deleterious inflammatory responses.

Cells, Cultured↗

Unilateral hydronephrosis in infants: are measurements of contralateral renal length useful?

PURPOSE: We investigated whether measurement of contralateral renal length in newborns with unilateral hydronephrosis may help to assess clinically significant hydronephrosis in the affected kidney. MATERIALS AND METHODS: We reviewed our experience with 53 newborns who had unilateral hydronephrosis presumed secondary to ureteropelvic junction obstruction. We divided the patients according to the presence of mild hydronephrosis and no obstruction on a furosemide renogram, severe hydronephrosis and obstruction on a furosemide renogram or a unilateral multicystic kidney. RESULTS: We found no significant correlation between findings on the affected and opposite normal sides. Contralateral hypertrophy, hypotrophy and normal sized kidneys were frequent findings. CONCLUSIONS: We conclude that measurement of contralateral renal length is not helpful in the evaluation of newborns with unilateral hydronephrosis.

Humans↗

Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis.

The induction of macrophage-deactivating (interleukin-10 [IL-10] and transforming growth factor beta [TGF-beta] and macrophage-activating (IL-1, IL-6, and tumor necrosis factor alpha [TNF-alpha] cytokines by lipoarabinomannan (LAM) from pathogenic Mycobacterium tuberculosis Erdman and H37Rv strains (ManLAM) and nonpathogenic mycobacteria (AraLAM) in human blood monocytes was examined. ManLAM was significantly less potent in induction of TNF-alpha, IL-1, IL-6, and IL-10 protein and mRNA, whereas its ability to induce TGF-beta was similar to that of AraLAM. Differences in induction of TNF-alpha mRNA by the two LAM preparations only became apparent at late time points of culture (24 h). The induction of TNF-alpha and IL-1 by purified protein derivative of M. tuberculosis was significantly stronger than that by ManLAM. Pretreatment of monocytes with ManLAM did not, however, interfere with cytokine induction by lipopolysaccharide or AraLAM. The extensive mannosyl capping of arabinose termini of ManLAM may underlie the lack of ability to induce some cytokines (IL-1, TNF-alpha, and IL-10) and the retained ability to induce TGF-beta. The latter may have a role in shifting the cytokine milieu in favor of survival of M. tuberculosis.

Animals↗