Jacob Freedman

Chapter 4 Coexistence of neuronal messengers — an overview

Publisher Summary This chapter discusses results demonstrating that neurons often contain more than one chemical compound. The different types of coexistence situations are described, including (1) a classical transmitter and one or more peptides, (2) more than one classical transmitter, and (3) a classical transmitter, a peptide, and adenosine triphosphate (ATP). The functional significance of these histochemical findings is at present difficult to evaluate, but in studies on the peripheral nervous system evidence has been obtained that classical transmitter and peptide are coreleased and interact in a cooperative way on effector cells. In addition to enhancement, there is evidence that other types of interactions may occur—for example, the peptide may inhibit the release of the classical transmitter. Also in the central nervous system (CNS), indirect evidence is present for similar mechanisms—that is, to strengthen transmission at synaptic (or non-synaptic) sites and for the peptide inhibition of release of a classical transmitter. Multiple messengers may provide the means for increasing the capacity for information transfer in the nervous system.

Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: Results from a randomized, multicenter study

BACKGROUND Covered biliary metal stents have been developed to prevent tumor ingrowth. Previous comparative studies are limited and often include few patients. OBJECTIVE To compare differences in stent patency, patient survival, and complication rates between covered and uncovered nitinol stents in patients with malignant biliary obstruction. DESIGN Randomized, multicenter trial conducted between January 2006 and October 2008. SETTING Ten sites serving a total catchment area of approximately 2.8 million inhabitants. PATIENTS A total of 400 patients with unresectable distal malignant biliary obstruction. INTERVENTIONS ERCP with insertion of covered or uncovered metal stent. Follow-up conducted monthly for symptoms indicating stent obstruction. MAIN OUTCOME MEASUREMENTS Time to stent failure, survival time, and complication rate. RESULTS The patient survival times were 116 days (interquartile range 242 days) and 174 days (interquartile range 284 days) in the covered and uncovered stent groups, respectively (P = .320). The first quartile stent patency time was 154 days in the covered stent group and 199 days in the uncovered stent group (P = .326). There was no difference in the incidence of pancreatitis or cholecystitis between the 2 groups. Stent migration occurred in 6 patients (3%) in the covered group and in no patients in the uncovered group (P = .030). LIMITATIONS Randomization was not blinded. CONCLUSIONS There were no significant differences in stent patency time, patient survival time, or complication rates between covered and uncovered nitinol metal stents in the palliative treatment of malignant distal biliary obstruction. However, covered stents migrated significantly more often compared with uncovered stents, and tumor ingrowth was more frequent in uncovered stents.

Antinociceptive and 'neurotoxic' actions of somatostatin in rat spinal cord after intrathecal administration

&NA; In the present investigation, the antinociceptive effect of somatostatin (SST) was assessed after intrathecal injection in rats. It was found that the peptide caused antinociception, hind limb paralysis and neuronal damage of the spinal cord in a dose‐dependent manner. The threshold dose for antinociception was lower (approximately 10 &mgr;g) than that (approximately 30 &mgr;g) giving rise to chronic motor impairment associated with necrotic changes and loss of an immunohistochemical marker for motoneurons in the spinal cord. It is concluded that the ‘ neurotoxic’ potential of SST should be considered in further clinical trials.

Antinociceptive Effects and Spinal Cord Tissue Concentrations after Intrathecal Injection of Guanfacine or Clonidine into Rats

In the present study, the antinociceptive effects of intrathecal injections of the α2-adrenoceptor agonists clonidine and guanfacine in rats was determined to establish their dose-response curves. Spinal cord tissue concentrations were also determined in a separate group of animals. Guanfacine was found to be more potent than clonidine and had a considerably longer duration of action. Thus, whereas the analgesic effect of clonidine declined to baseline by 4 hr after injecting doses of up to 50 μg, guanfacine still showed a considerable effect 18 hr after injecting both 25 and 50 μg. With both compounds, concentration gradients existed within the spinal cord. In the experiments with guanfacine, the region in the spinal cord tissue with the highest concentrations 10 min after injection contained around 30 pmollmg wet weight. At 3 hr, this figure was around 20 pmollmg. With clonidine, on the other hand, the concentration decreased from the maximal level of 200 pmollmg at 10 min to 10 pmollmg at 3 hr. On all occasions, except 10 min after injecting clonidine, it was found that the maximal tissue concentrations for both drugs remained below the cervical spinal cord, i.e., the rostral spread was less than expected, especially with drugs with such a long duration of action. The present investigation demonstrates analgesic effects of both clonidine and guanfacine after intrathecal administration, with guanfacine proving more potent and longer acting; the difference in duration of action is probably attributable to differences in rates of elimination of the drugs from spinal cord tissue.

Antiobesity surgery in Sweden from 1980 to 2005: a population-based study with a focus on mortality.

Background:Antiobesity surgery reduces mortality, but this reduction is dependent to a great extent on surgical perioperative mortality. Population-based perioperative mortality after antiobesity surgery is not well known. Objective:To evaluate mortality after antiobesity surgery in Sweden. Design:Retrospective cohort study. Setting:All patients who underwent antiobesity surgery in Sweden between 1980 and 2005. Main Outcome Measures:All-cause mortality after antiobesity surgery. Results:A total of 12,379 patients (9,614 women) with mean age (±SD) of 39.5 ± 10.4 years underwent 14,768 antiobesity procedures. Mean follow-up time was 10.9 ± 6.3 years. A total of 751 (6.1%) patients died during the follow-up period and the cumulative 30-day, 90-day, and 1-year mortality was 0.2, 0.3, and 0.5%, respectively. Early cumulative mortality was higher for men and patients older than 50 years of age. Long-term mortality was higher in men than in women (90 vs. 50 per 10,000 person years when excluding early deaths, mortality rate ratio 1.8 (95% CI, 1.5–2.1)). There was no difference in the rates of early mortality when primary procedures were compared with reoperations. Myocardial infarction and malignancy were the most common late causes of death after surgery. Conclusions:Antiobesity surgery can be performed safely in unselected populations of obese patients with low rates of early mortality. Men are at a higher risk of early death, which is carried through over long-term follow-up, and that is why a future specific study of the effect of antiobesity surgery on mortality in men is warranted.

High revision rates after laparoscopic vertical banded gastroplasty

BACKGROUND To evaluate, in a surgical department at a university hospital in Stockholm, Sweden, the long-term results after laparoscopic vertical banded gastroplasty (VBG), with special emphasis on revisional surgery. Few studies are available with long-term results after laparoscopic VBG. Some short-term studies have shown results similar to gastric banding. METHODS All consecutive patients who underwent attempted laparoscopic VBG between 1995 and 2005 were followed up regarding weight loss and the need for revisional surgery. Follow-up was from the date of surgery to the end of the observational period (December 2006). RESULTS In 486 patients, laparoscopic VBG was attempted. Of the 486 cases, 64 were converted to open surgery. Conversions were common in the first patients, with a conversion rate of 4% during the last 100 patients. The mean body mass index at surgery was 42.4 kg/m2. The median follow-up was 3 years (range 0-11). All patients lost weight. A total of 104 patients (21%) required revisional surgery 114 times during the follow-up period, with food intolerance/vomiting and insufficient weight loss the most common reasons. Of the 104 patients, 31 underwent repeat VBG, of whom 10 needed a secondary revisional procedure, and 49 required conversion to gastric bypass, of whom none have required additional revisional surgery. CONCLUSION Laparoscopic VBG is associated with high revisional rates. In the case of failed VBG, repeat VBG seems to be a poor option and conversion to gastric bypass yields better results. We have abandoned VBG as a surgical option in the treatment of obesity.

Three-Year Results of Laparoscopic Vertical Banded Gastroplasty

Background: Despite the development of pharmacologic agents for the treatment of massive obesity, surgery remains the only treatment option that has been shown to offer long-term weight reduction. Laparoscopic surgery appears to offer rapid recovery and low postoperative morbidity. The aim of the present study was to assess the outcome of laparoscopic vertical banded gastroplasty (lap VBG) in 60 obese patients. Patients and Methods: 60 massively obese patients (50 female) with a mean ± SEM body mass index (BMI) of 44.4 ± 1.0 kg/m2 were followed up prospectively for an average of 23.0 ± 1.5 months. Lap VBG was performed using 5 trocars placed in a standard fashion for laparoscopic upper gastrointestinal surgery. A 4-row stapler was used for the vertical staple-line, and a stretched polytetrafluoroethylene (Gore-Tex) band was used to reinforce the outlet. The patients were seen postoperatively 2, 6, 12, 24, and 36 months after surgery. Results: Conversion to open surgery was performed in 15 cases. Preoperative median BMI and postoperative hospital stay were higher in the open group than in the laparoscopic group: 47.8 kg/m2 (37.7-65.7) and 5 days (3-13), and 41.9 kg/m2 (32.5-57.3) and 3 days (2-6), respectively (P < 0.01 for both). After 36 months of follow-up, the median BMI was 36.9 kg/m2 (24.6-50.7) (n = 9) in the open group and 37.0 kg/m2 (25.8-53.3) (n = 14) (NS) in the laparoscopic group. The number of conversions to open surgery and the median operating time were higher in the first 30 cases than in the last 30 cases: 11 and 137.5 min (96-225) and 4 and 115.0 min (85-190), respectively, with similar preoperative BMI: 44.1 kg/m2 (33.8-65.8) and 41.2 kg/m2 (32.4-57.8). Conclusions: Lap VBG can be performed safely and results in a shorter postoperative stay than does open surgery. Weight loss was maintained over the 3-year follow-up period. There is a learning curve, resulting in fewer conversions to open surgery and shorter operating time. Long follow-up studies are needed to ascertain that long-term weight loss equals that of open VBG.

Thyrotropin-releasing hormone (TRH) counteracts neuronal damage induced by a substance P antagonist

SummaryIntrathecal administration of the substance P antagonist Spantide caused marked necrotic changes of the gray matter of the spinal cord extending several segments from the injection site. Intravenous treatment with several doses of thyrotropin releasing hormone before and after Spantide injection completely prevented the necrotic lesion.

Bariatric surgery reduces mortality in Swedish men

Mortality is lower in obese patients who have undergone surgery for obesity than in those who have not. The majority of patients in these studies have been women. Perioperative mortality is known to be higher among men, and this may counterbalance the survival advantage seen after surgery. This cohort study compared mortality among operated obese patients, non‐operated obese patients and a general control cohort of men.

Five-Year Results of Laparoscopic Vertical Banded Gastroplasty in the Treatment of Massive Obesity

Background: Laparoscopic surgery appears to offer rapid recovery and low postoperative morbidity.The aim of the present study was to assess the outcome of laparoscopic vertical banded gastroplasty (LVBG) in 154 obese patients with a follow-up of 12-60 months. Patients and Methods: 154 massively obese patients (132 female) with a mean ±SEM body mass index (BMI) of 43.4±0.6 kg/m2 were followed prospectively for an average of 31.7±1.4 months. LVBG was performed using 5 trocars placed in a standard fashion for laparoscopic upper gastrointestinal surgery. A 4-row stapler was used for the vertical staple-line and a stretched polytetrafluoroethylene (Gore-tex®) band was used to reinforce the outlet. After the first 67 cases, the procedure was altered so that a 5-cm length was marked on the band. Results: Conversion to open surgery was performed in 33 cases. All patients lost weight. At 60 months follow-up, the postoperative weight was similar in the open and laparoscopic group.The subjects where 5 cm length was marked on the band had a significantly better weight loss at 36 months (30.4 ±1.2). Both early (<1 month postoperative) and late (>1 month postoperative) complications were more common in the group converted to open surgery. Postoperative stay was shorter in the laparoscopic group. Conclusions: LVBG can be performed safely and results in shorter postoperative stay than openVBG. With adherence to surgical technique (5-cm band circumference), weight-loss is maintained at an adequate level. Complications after LVBG do not exceed open VBG.