Intra-Abdominal Cooling System Limits Ischemia-Reperfusion Injury During Robot-Assisted Renal Transplantation.

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follows: Robotic renal transplantation with (n = 11) and without (n = 6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n = 6). Renal cortex temperature, magnetic resonance imaging, and histology were analyzed. Robotic renal transplantation required a longer anastomosis time, either with or without the cooling system, compared to the open approach (70.4 ± 17.7 min and 74.0 ± 21.5 min vs. 48.7 ± 11.2 min, p-values < 0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5 ± 3.1°C vs. 22.5 ± 6.5°C; p = 0.001) or compared to the robotic group without the cooling system (28.7 ± 3.3°C; p < 0.001). Magnetic resonance imaging parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the noncontrolled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries.

Robotic general surgery: current practice, evidence, and perspective.

BACKGROUND: Robotic technology commenced to be adopted for the field of general surgery in the 1990s. Since then, the da Vinci surgical system (Intuitive Surgical Inc, Sunnyvale, CA, USA) has remained by far the most commonly used system in this domain. The da Vinci surgical system is a master-slave machine that offers three-dimensional vision, articulated instruments with seven degrees of freedom, and additional software features such as motion scaling and tremor filtration. The specific design allows hand-eye alignment with intuitive control of the minimally invasive instruments. As such, robotic surgery appears technologically superior when compared with laparoscopy by overcoming some of the technical limitations that are imposed on the surgeon by the conventional approach. PURPOSE: This article reviews the current literature and the perspective of robotic general surgery. CONCLUSIONS: While robotics has been applied to a wide range of general surgery procedures, its precise role in this field remains a subject of further research. Until now, only limited clinical evidence that could establish the use of robotics as the gold standard for procedures of general surgery has been created. While surgical robotics is still in its infancy with multiple novel systems currently under development and clinical trials in progress, the opportunities for this technology appear endless, and robotics should have a lasting impact to the field of general surgery.

[Robotic-assisted organ transplantation]. / Transplantation d'organes avec assistance robotique.

Advanced surgical procedures have traditionally been a domain of open surgery. However, minimally invasive approaches are evolving with the development of robotic technology which appears capable to overcome technical limitations of conventional laparoscopy. While traditionally perceived as impossible indications for minimally invasive surgery, reports on robotic organ transplantations have surfaced with promising results.

Robotic distal pancreatectomy: a valid option?

Although reported in the literature, conventional laparoscopic approach for distal pancreatectomy is still lacking widespread acceptance. This might be due to two-dimensional vision and decreased range of motion to reach and safely dissect this highly vascularized retroperitoneal organ by laparoscopy. However, interest in minimally invasive access is growing ever since and the robotic system could certainly help overcome limitations of the laparoscopic approach in the challenging domain of pancreatic resection, notably in distal pancreatectomy. Robotic distal pancreatectomy with and without spleen preservation has been reported with encouraging outcomes for benign and borderline malignant disease. As a result of upgraded endowristed manipulation and three-dimensional visualization, improved outcome might be expected with the launch of the robotic system in the procedure of distal pancreatectomy. Our aim was thus to extensively review the current literature of robot-assisted surgery for distal pancreatectomy and to evaluate advantages and possible limitations of the robotic approach.

Preclinical cadaveric study of transanal endoscopic da Vinci® surgery.

BACKGROUND: Single-port platforms are increasingly being used for transanal surgery and may be associated with a shorter learning curve than transanal endoscopic microsurgery. However, these procedures remain technically challenging, and robotic technology could overcome some of the limitations and increase intraluminal manoeuvrability. An initial experimental experience with transanal endoscopic da Vinci(®) surgery (TEdS) using a glove port on human cadavers is reported. METHODS: After initial dry laboratory experiments, the feasibility of TEdS and ideal set-up were further evaluated in human cadavers. For transanal access a glove port was constructed on-table by using a circular anal dilator, a standard wound retractor and a surgical glove. A da Vinci(®) Si HD system was used in combination with the glove port for transanal endoscopic resections. RESULTS: It was possible to perform all necessary tasks to complete a full-thickness excision and closure of the rectal wall, with cadavers in both prone and supine positions. The stable magnified view, combined with the EndoWrist(®) technology of the robotic instruments, made every task straightforward. Intraluminal manoeuvrability could be improved further by intersecting the robotic instruments. The glove port proved to be very reliable and the inherent flexibility of the glove facilitated docking of the robotic arms in a narrow confined space. CONCLUSION: Using a reliable and universally available glove port, TEdS was feasible and a preferred set-up was determined. Further clinical trials will be necessary to assess the safety and efficacy of this technique.

[Robotic single site surgery: current practice and future developments]. / Chirurgie robotique par incision unique: pratique actuelle et futurs développements.

Robotic surgery has been gaining increasing acceptance for several years now, establishing itself with success in all the surgical fields. Besides, since the introduction of single site surgery, the interest for the robotic technology is more than obvious, offering technical possibilities to overcome the natural limitations of laparoscopy. This article reviews the different devices available and the indications of robotic single site surgery. Moreover, the future developments of this new technology are discussed as well.

The Impact of Pregnancy on Outcomes After Bariatric Surgery.

BACKGROUND: Bariatric surgery is performed mostly on obese women of reproductive age. Many studies have analyzed pregnancy outcomes after bariatric surgery, but only a small number have studied the impact of pregnancy on the postoperative outcomes. PURPOSE: To study the effect of pregnancy on outcomes after bariatric surgery in women of childbearing age. METHODS: From January 2010 to October 2017, a retrospective study of a prospectively maintained database was conducted at the University Hospital of Geneva (HUG), where 287 women between the ages of 18 and 45 years had undergone Roux-en-Y gastric bypass (RYGB). A comparison of the results during a 5-year follow-up was performed between women who became pregnant after their bariatric surgery (pregnancy group, n = 40) and postoperative non-pregnant women (non-pregnancy group, n = 247). The two groups were compared for weight loss, complications, and nutritional deficiencies. RESULTS: The pregnancy group was significantly younger (29.2 ± 5.5 vs. 36.4± 6.3 years, p < 0.001) and heavier (124.0 ± 18.0 kg vs. 114.7 ± 17.1, p < 0.001) compared with the non-pregnancy group at the time of surgery. The percentage of excess BMI loss (%EBMI loss) was similar in both groups during the 5-year follow-up. Complications after RYGB and nutritional deficiencies were nearly identical in the two groups. The interval of time between bariatric surgery and first pregnancy was a median of 20.8 months. Out of 40 first pregnancies, 28 women completed pregnancy successfully with live birth. CONCLUSION: Pregnancy after bariatric surgery is safe and does not adversely affect outcomes after RYGB.

Amyand's hernia: 10 years' experience.

BACKGROUND: Amyand's hernia is an atypical groin hernia which contains the vermiform appendix. The aim of this study was to review a single institution's experience in the clinical presentation, management and prognostic factors of this rare hernia. METHODS: The authors reviewed records of all patients undergoing hernia surgery from 1996 to 2006 at their institution, a tertiary care, University-affiliated hospital. RESULTS: Twelve patients (six men) with a median age of 88 years (range 60-97) were included. Six presented with right inguinal hernias and six presented with right femoral hernias. All required emergency surgery: eight for strangulated hernias, two for hernias with lower quadrant peritonism and two for incarcerated hernia. Despite small differences in outcome and length of hospitalisation between Amyand types, appendix inflammation, pre-operative blood examinations and hernia localisation, only right lower quadrant peritonism as a presenting sign (p=0.004) and age greater than 90 years old (p=0.04) were significantly associated with a poor outcome. CONCLUSION: Amyand's hernia is a rare hernia which is seldom diagnosed before operation. It must be considered in the evaluation of a strangulated or incarcerated hernia. Further studies are required to define the optimal surgical strategy, prognostic factors and risks of hernia recurrence.

Cosmetic issues of abdominal surgery: results of an enquiry into possible grounds for a natural orifice transluminal endoscopic surgery (NOTES) approach.

BACKGROUND AND STUDY AIMS: Decreased scarring is an advantage of minimally invasive surgery. The new experimental technique of natural orifice transluminal surgery (NOTES) aims at totally scarless surgery. We examined the general attitudes of patients and unaffected persons towards scarless surgery. METHODS AND PARTICIPANTS: We used a 7-item questionnaire in structured interviews with hospital visitors, following detailed standardized explanation of terms used and of possible complications, to groups of 10 participants, during an "open ward" day. A visual analog scale (VAS) from 1 (none) to 10 (very much) was used for all but one item. Questions concerned the importance of cosmetic results in abdominal surgery, satisfaction regarding existing scars, hypothetical acceptance of increased risk as a trade-off for the absence of scars, and other issues. Data were analyzed for participants overall, and for three age groups and both sexes. RESULTS: 292 participants (male : female 1 : 1; mean age 43 years) completed the questionnaire. Cosmetic issues were rated as important (median 8), but acceptance of existing scars was also high in those affected (median 8, n=68). Approval of scarless surgery decreased with a presumed risk increase (from score 9 down to score 5), and overall an increase in risk of 10 % was judged to be acceptable as a trade-off for total absence of scarring. Younger people tended to be less satisfied with scars, but were also less inclined than older people to accept higher surgical risk in this hypothetical context. CONCLUSIONS: People generally seem to favor scarless abdominal surgery, even with some increase in risk.

Hybrid natural orifice transluminal endoscopic surgery (NOTES) for Roux-en-Y gastric bypass: an experimental surgical study in human cadavers.

BACKGROUND AND STUDY AIMS: The advantages of a hybrid natural orifice transluminal endoscopic surgery approach to Roux-en-Y gastric bypass (hNOTES-RYGBP) might include: easier access to the peritoneal cavity, reduced number of ports and related complications, improved cosmesis, and others. However, currently available conventional endoscopic and laparoscopic instruments might be unsuitable for complex surgical procedures using transluminal access. The aim of this study was to investigate the feasibility and limitations of a NOTES RYGBP. METHODS: hNOTES-RYGBP was performed in human cadavers. Pouch creation was achieved by needle-knife dissection using a transvaginal, flexible scope. Articulating linear staplers were placed transumbilically to transect the stomach. Measurements of the small bowel were accomplished intraluminally or with flexible and rigid graspers. New methods were tested to create the gastro-jejunal anastomosis. A linear laparoscopic stapler was used to form the jejuno-jejunal anastomosis. RESULTS: Stapler manipulation and anvil docking, bowel manipulation and measurement, and tissue dissection presented the main obstacles for hNOTES-RYGBP. Conventional instruments were too short for some transvaginal manipulations. The time to complete the procedure was 6 - 9 hours. It was feasible to perform a complete hNOTES-RYGBP in four out of seven cadavers. Two cadavers were unsuitable due to anatomical abnormalities or advanced decay. One procedure was terminated before completion because of time constraints. Combinations of flexible and rigid visualization and manipulation were helpful, especially for dissection and gastric pouch creation. CONCLUSIONS: Several factors made hNOTES-RYGBP very challenging and time-consuming. A lack of proper instrumentation resulting in insufficient tissue traction, countertraction, and instrument manipulation complicated several steps during the procedure. A combination of flexible with rigid endoscopic techniques offers specific advantages for components of this type of surgery. Changes in instrument design are required to improve more complex endosurgical procedures.

Visual clues act as a substitute for haptic feedback in robotic surgery.

OBJECTIVE: The lack of haptic feedback (HF) in robotic surgery is one of the major concerns of novice surgeons to that field. The superior visual appearances acquired during robotic surgery may give clues that make HF less important. METHODS: We surveyed 52 individuals on their perception of HF during robotic surgery. The first group of 34 surgically inexperienced people used the da Vinci robot for their first time (drylab). The second group included 8 laparoscopic surgeons with experience up to a fifth robotic operation. The third group included 10 surgical experts with substantial experience (150-650 robotic cases). Visual analog assessment was made of perception of HF, how much HF was missed, how much the absence of HF impaired the operators' level of comfort. Robotic experts were asked if complications have occurred as a result of a lack of HF. RESULTS: Of the first group, 50% reported the perception of HF, as did 55% of the second group and 100% of the third group (difference between group 1 and group 3: p < 0.05). The first group missed HF for 6.5; the second group for 4.3, and the third group for 4 (difference between groups 1 and 3: p < 0.05). The surgical experts claimed to have missed HF for 7.2 s when they first started robotic surgery (Difference to now: p < 0.05). The lack of HF caused discomfort for the first group of 4; for the second group of 4,4, and for the third group of 2,6. One complication was reported by the robotic experts as resulting from the lack of HF. CONCLUSIONS: The data support the conclusion that even beginners quickly experience the perception of HF when performing robotic surgery. With more experience, perception of HF and the level of comfort with robotic surgery increases significantly. This perception of HF makes "real" HF less important and demonstrates that its importance is overestimated by novices in robotic surgery.

Incisional hernia after robotic single-site cholecystectomy: a pilot study.

PURPOSE: Robotic LaparoEndoscopic Single-Site Surgery Cholecystectomy has been performed for 5 years using a dedicated platform (da Vinci® Single-Site®) with the da Vinci® Surgical System (Intuitive Surgical Inc., Sunnyvale, CA, USA). While short-term feasibility has been described, long-term assessment of this method is currently outstanding. The aim of this study was to assess long-term parietal complications of this technique. METHODS: In this retrospective study, patients operated between 2011 and 2013 were evaluated. Parietal incision was assessed with ultrasonography and patients screened for residual pain from scar tissue. Demographic and perioperative data were also collected. RESULTS: We evaluated 48 patients [38 female, 79.2%; median age 49 years (range: 24-81 years)]; mean BMI 25.9 kg/m2 [±SD 4.1 kg/m2]. After a median follow-up of 39 months (range: 25-46 months), six incisional hernias (two patients had a positive echography but a negative clinical examination) were found (12.5%, 95% CI 7.5-30.2), and two patients had a surgical repair. The overall rate of incisional hernia was 16.7% (95% CI 7.5-30.2). Residual pain was observed in 5 of 48 patients. CONCLUSION: This preliminary study suggests that a clinically significant rate of incisional hernias can occur after R-LESS-C. Larger studies comparing R-LESS-C to alternative methods with long-term follow-up are necessary.

Synthesis and antiviral activity of enantiomeric forms of cyclobutyl nucleoside analogues.

The syntheses of the enantiomeric cyclobutyl guanine nucleoside analogues [1R-1 alpha, 2 beta, 3 alpha]- and [1S-1 alpha, 2 beta, 3 alpha]-2- amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one (7 and 8, respectively) and the enantiomeric cyclobutyl adenine analogues [1R-1 alpha, 2 beta, 3 alpha]- and [1S-1 alpha, 2 beta, 3 alpha]-6-amino-9-[2,3-bis(hydroxymethyl) cyclobutyl]purine (9 and 10, respectively) are described. trans-3,3-Diethoxy-1,2-cyclobutanedicarboxylic acid (14) was coupled with R-(-)-2-phenylglycinol to provide a mixture of diastereomeric bis-amides, 15a and 15b, which was readily separated by crystallization. Conversion of each bis-amide to the corresponding diol enantiomer, 16a and 16b, respectively, was effected by a facile three-step sequence in high overall yield. Homochiral diol 16a was converted in a straightforward manner to 7 and 9, and homochiral diol 16b was similarly converted to the corresponding optical isomers 8 and 10. Compounds 7 and 9, which mimic the absolute configuration of natural nucleosides, are highly active against a range of herpesviruses in vitro while the isomers of opposite configuration, 8 and 10, are devoid of antiherpes activity. The corresponding triphosphates of 7 and 8 (7-TP and 8-TP) were prepared enzymatically. Compound 7-TP selectively inhibits HSV-1 DNA polymerase, compared to human (HeLa) DNA polymerase, while 8-TP is much less inhibitory than 7-TP against both types of enzymes. Compounds 7 and 9 are efficacious in a mouse cytomegalovirus model infection.

(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)-cyclobutyl] guanine [(+-)-BHCG or SQ 33,054]: a potent and selective inhibitor of herpesviruses.

(+-)-(1 alpha,2 beta,3 alpha)-9-[2,3-bis(hydroxymethyl)cyclobutyl] guanine [(+-)-BHCG or SQ 33,054] is a newly synthesized nucleoside analog with potent and selective antiviral activity against members of the herpesvirus group, including human cytomegalovirus. The activity against a thymidine kinase deficient HSV-2 mutant was 25-fold poorer than against the parent virus, suggesting that phosphorylation is an important prerequisite for antiviral activity against HSV-2. (+-)-BHCG is readily phosphorylated by purified HSV-1 thymidine kinase, and BHCG triphosphate synthesized enzymatically is a selective inhibitor of HSV-1 DNA polymerase. (+-)-BHCG did not inhibit host cell growth at concentrations at least 1000-fold higher than HSV-2 inhibitory concentrations. Subcutaneous administration of (+-)-BHCG was protective against HSV-1 systemic infections in mice. BHCG is an exciting antiviral agent and represents a new class of nucleoside analogs.

In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia.

Hyperargininemia is a metabolic disorder biochemically characterized by tissue accumulation of arginine and other guanidino compounds. Convulsions, lethargy and psychomotor delay or cognitive deterioration are predominant clinical features of this disease. Although neurologic symptoms predominate in this disorder, their pathophysiology is still unknown. In the present study we investigated the in vitro effects of arginine, N-acetylarginine, argininic acid and homoarginine on some oxidative stress parameters in rat brain in the hope to identify a possible mechanism for the brain damage in hyperargininemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the cerebral cortex of rats in the presence of various concentrations of these compounds. The results showed that all guanidino compounds tested significantly increased chemiluminescence and decreased TRAP at concentrations similar to those observed in the tissue of hyperargininemic patients. Furthermore, these compounds inhibited CAT and GSH-Px activities to varying extents, with GSH-Px activity being more susceptible to their action. In turn, argininic acid inhibited all enzyme activities, and its main action was also directed towards GSH-Px. The results suggest that oxidative stress caused by guanidino compounds may be involved in the brain dysfunction amongst other potential pathophysiological mechanisms observed in hyperargininemia.

Spin exchange optical pumping based polarized 3He filling station for the Hybrid Spectrometer at the Spallation Neutron Source.

The Hybrid Spectrometer (HYSPEC) is a new direct geometry spectrometer at the Spallation Neutron Source at the Oak Ridge National Laboratory. This instrument is equipped with polarization analysis capability with 60° horizontal and 15° vertical detector coverages. In order to provide wide angle polarization analysis for this instrument, we have designed and built a novel polarized (3)He filling station based on the spin exchange optical pumping method. It is designed to supply polarized (3)He gas to HYSPEC as a neutron polarization analyzer. In addition, the station can optimize the (3)He pressure with respect to the scattered neutron energies. The depolarized (3)He gas in the analyzer can be transferred back to the station to be repolarized. We have constructed the prototype filling station. Preliminary tests have been carried out demonstrating the feasibility of the filling station. Here, we report on the design, construction, and the preliminary results of the prototype filling station.

Robotic vs. laparoscopic Nissen fundoplication for gastro-oesophageal reflux disease: systematic review and meta-analysis.

The aim of this meta-analysis was to compare clinical outcome following laparoscopic and robotic Nissen fundoplication. A systematic literature search of Medline, Embase and Cochrane Library databases was performed. Primary outcome measures were the requirement for re-operation, postoperative mortality and postoperative dysphagia. Secondary outcome measures were operative time, length of hospital stay, operative complications and cost. Six randomized trials, of 226 patients, were included in this meta-analysis. There was no significant difference in requirement for re-operation or in postoperative dysphagia. There was a significantly reduced total operative time in the laparoscopic group (weighted mean difference = 4.154; 95% CI = 1.932-6.375; p = 0.0002). There was no significant difference between robotic and laparoscopic groups for hospital stay or operative complications. Clinical results from robotic Nissen fundoplication were comparable to the standard laparoscopic approach, but there was associated increased operative time and procedure cost.

Absolute myocardial blood flow determination using real-time myocardial contrast echocardiography during adenosine stress: comparison with single-photon emission computed tomography.

OBJECTIVE: To assess the feasibility and diagnostic accuracy of real-time myocardial contrast echocardiography (MCE)-derived absolute myocardial blood flow for detection of myocardial perfusion abnormalities compared with simultaneous technetium 99 m sestamibi single-photon emission computed tomography (SPECT). DESIGN: Prospective study. SETTING: Tertiary-care medical institution. PATIENTS: 79 patients with known or suspected coronary artery disease. INTERVENTIONS: Simultaneous SPECT and real-time MCE during adenosine stress. MAIN OUTCOME MEASURES: Absolute myocardial blood flow (MBF, ml/min/g), microbubble velocity (beta, min(-1)), and reserve values. Endpoints included sensitivity, specificity, positive likelihood ratio (LR+) or negative likelihood ratio (LR-) and area under the curve (AUC) of the receiver operating characteristic curve. RESULTS: Reserve measurements were feasible in 975 of 1343 segments (73%); of these, 130 segments (13%) were abnormal by SPECT. MCE perfusion parameters clearly distinguished abnormal from normal segments for beta reserve (1.13 (0.99) vs 2.22 (1.36), p<0.001) and MBF reserve (1.80 (2.29) vs 3.69 (2.79), p<0.001). The beta reserve cut-off of 1.60 provided the following: AUC, 0.787; sensitivity, 82%; specificity, 66%; LR+, 2.40; and LR-, 0.28. The MBF reserve cut-off of 1.90 provided the following: AUC, 0.779; sensitivity, 73%; specificity, 72%; LR+, 2.69; and LR-, 0.37. MBF reserve had an AUC of 0.773 for the left anterior descending coronary artery, 0.885 for the left circumflex coronary artery and 0.739 for the right coronary artery. CONCLUSIONS: Real-time MCE-derived absolute MBF, beta, and reserve values are feasible and accurate for detecting myocardial perfusion abnormalities as defined by SPECT.

Inhibition of herpes simplex virus type 1 DNA polymerase by [1R(1 alpha,2 beta,3 alpha)]-9-[2,3-bis(hydroxymethyl)cyclobutyl] guanine.

(+/-)-(1 alpha,2 beta,3 alpha)-9-[2,3-Bis(hydroxymethyl)cyclobutyl] guanine [(+/-)-BHCG] is a nucleoside analog with potent in vitro activity against herpesviruses [Tetrahedron Lett. 30:6453-6456 (1989)]. The two enantiomers have been synthesized, and their biochemical characterization is reported here. [1S(1 alpha,2 beta,3 alpha)]-9-[2,3-Bis(hydroxymethyl)cyclobutyl]guanine [(S)-BHCG] was phosphorylated by herpes simplex virus type 1 (HSV-1) thymidine kinase (Vmax = 8 nmol/hr/micrograms of enzyme), whereas [1R(1 alpha,2 beta,3 alpha)]-9-[2,3-bis(hydroxymethyl)cyclobutyl]guanine [(R)-BHCG] was a poor substrate for the viral thymidine kinase under these conditions. The triphosphate of each enantiomer was enzymatically synthesized, and both enantiomers competitively inhibited HSV-1 DNA polymerase with respect to dGTP. However, the potency of (R)-BHCG-TP was 4 orders of magnitude greater than that of (S)-BHCG-TP. (R)-BHCG-TP inhibited HeLa DNA polymerase alpha, but the inhibition constant was 30-fold higher than that for the viral DNA polymerase. In comparison, (S)-BHCG-TP was a very poor inhibitor of DNA polymerase alpha. (R)-[3H]BHCG-TP could be incorporated into a synthetic DNA template by HSV-1 DNA polymerase at 80% the extent of dGTP under the assay conditions used and, therefore, could act as an alternative substrate. Incorporation of (R)-BHCG-TP was similar to that observed for acyclovir triphosphate and ganciclovir triphosphate, based on maximal velocities. In contrast, HSV-1 DNA polymerase did not incorporate (S)-BHCG-TP into DNA. Compared with dGTP, only limited extension (10%) of the DNA primer by HSV-1 DNA polymerase occurred after incorporation of (R)-BHCG-TP and, therefore, (R)-BHCG-TP acts as a nonobligate chain terminator.