Tropane alkaloid production in transformed root cultures of brugmansia Candida

Transformed root cultures of BRUGMANSIA CANDIDA were established by infection with AGROBACTERIUM RHIZOGENES LBA 9402. Several clones with different growth index and tropane alkaloid pattern and content were obtained and two were examined in depth. The alkaloid content and pattern changed during the time course. At 21 days of culture clone 1 revealed an alkaloid spectrum dominated by 3alpha-acetoxytropane (about 50% of the total alkaloid) and hyoscyamine (about 25%), with a ratio of hyoscyamine to scopolamine of 11.2. In clone 40 this ratio was 1.5 and the content of 3alpha-acetoxytropane was low (2%). The maximum concentrations of hyoscyamine were obtained at 3 weeks of culture, and were 700 and 500 microg/g FW in clone 1 and 40, respectively.     

Nicotine: therapeutic potential for the treatment of ulcerative colitis

Ulcerative colitis (UC) is predominantly a disease of non-smokers, and nicotine may be the agent responsible for this association. Transdermal nicotine has been shown to improve disease activity and sigmoidoscopic appearance in the active disease but in one study had no effect on maintenance of remission. Since side-effects with nicotine patches occur in up to two thirds of patients, attempts to reduce systemic levels and improve drug tolerance have been developed with colonic delivery systems of nicotine. Preliminary observations with nicotine enemas in UC have shown clinical benefit, but controlled trials are needed. Mechanisms responsible for the association of smoking with colitis and for the therapeutic effect of nicotine remain an enigma; possibilities include: modulation of the immune response, alterations of colonic mucus and eicosanoid production, changes in rectal blood flow, decreased intestinal permeability and the release of endogenous glucocorticoids. With current treatment for UC limited to corticosteroids and formulations of 5-aminosalicylic acid, alternative treatments are required and nicotine may fulfil this role.     

The immunomodulatory actions of E-type prostaglandins

Prostaglandins (PGs) have been recognised as modulators of immune responses. This has been proved by both in vitro studies and from observations in animals and humans. Administration of prostaglandins for therapeutic purposes, however, has been hampered by their limited bioavailability and their pleiotropic effects, with resultant toxicological profile. Despite this, some success has been demonstrated in the clinic for the control of graft rejection, especially when used as part of a broader immunosuppressant regimen. Full realisation of the therapeutic potential of prostaglandins will depend on a better understanding of their mechanism of action at the cellular level. Recently, it has been appreciated that prostaglandins do not merely inhibit T-cell function, but appear to modulate the profile of lymphocyte sub-populations through regulation of cytokine synthesis and release. Recent efforts have also begun to focus on identifying prostaglandin receptor subtypes important for immune regulation and offer a means, together with targeted delivery, of utilising the immunosuppressant/anti-inflammatory effects of E-type prostaglandins in a safe and effective manner.     

Gender differences in the use of outpatient mental health services

Current economic constraints necessitate careful planning and evaluation of mental health services. Gender differences in need and use of outpatient mental health services are synthesized based on current epidemiological research. Although overall prevalence rates of mental disorder are similar, women use more outpatient mental health services than do men. This disparity exists largely within the primary care sector. The study of social roles and behavior may help explain these gender differences. Implications for planning and organizing outpatient mental health services are discussed.     

Is the IV obstructed or infiltrated? A simple clinical test

Objective. The objective of our study was to determine if clinical observation of pressure-flow relationships (PFR) can differentiate between partial external obstruction (obstruction) and infiltration as a cause of poor performance of gravity-fed infusions.Methods. A total of 24 patients with functional intravenous cannulae in situ had obstruction simulated by the application of a tourniquet proximal to the cannula. The change in flow (F) for a discrete change in pressure (P) was determined in each case by counting drop rates at two different elevations of the fluid reservoir level, 10 cm apart. The same process was repeated in 15 patients in whom the cannula was in an extra vascular location (infiltration). Three sizes of cannula—16-gauge, 18-gauge, and 20-gauge—were examined, with equal distribution of sizes in each group. The effect on flow rates of inflating a blood pressure (BP) cuff proximally on the cannulated limb was assessed. The ratio P/F is the total resistance of the infusion system, and by subtracting known values for resistance of infusion tubing and cannula, the venous or tissue resistance was calculated.Results. There was a statistically significant difference between the change in flow for obstructed compared with infiltrated cannulae for the same change in pressure for each cannula size. The mean venous resistance was 23 mm Hg/L/hr, while that of tissue was 280 mm Hg/L/hr, with no overlap between groups. There was no effect on flow rate with blood pressure cuff inflation in the infiltrated group whereas flow progressively fell in the obstructed group.Conclusions. Clinical observation of PFRs in poorly functioning gravity-fed IV infusions can assist in detecting infiltration as a cause. Inflation of a blood pressure cuff will further impair flow where the cannula is intravascular, but will have no effect in an extravascular location.     

Hypothalamo-pituitary-adrenal cortical responses to low-dose physostigmine and arginine vasopressin administration: sex differences between major depressives and matched control subjects

Of heuristic value in understanding the neurochemistry of major depression is whether the hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity that occurs in this illness can be related to putative neurotransmitter dysfunction(s). Cholinergic neurotransmission stimulates hypothalamic corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) secretion, both of which stimulate pituitary corticotropin (ACTH) secretion, but whether the HPA axis in humans is activated only by doses of cholinergic agonists that produce noxious side effects remains controversial. To test the hypothesis of increased cholinergic sensitivity in major depression, physostigmine (PHYSO), a reversible cholinesterase inhibitor, was administered to patients and control subjects at a dose that elevated plasma ACTH, cortisol, and AVP concentrations but produced few or no side effects. Exogenous AVP also was administered to determine if it would augment the effect of low-dose PHYSO on the HPA axis. Twelve premenopausal or estrogen-replaced female major depressives, 12 individually matched female control subjects, eight male major depressives, and eight matched male control subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV), AVP (0.08 U/kg IM), PHYSO + AVP, and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for ACTH1-39, cortisol, and AVP. Estradiol and testosterone were also measured at each test session. PHYSO (8 microg/kg) significantly increased plasma ACTH, cortisol, and AVP, while producing no side effects in approximately half the subjects and predominantly mild side effects in the other half. These hormone increases following PHYSO occurred primarily in the female depressives and the male control subjects and were not significantly related to the presence or absence of side effects. The greater the ACTH and AVP responses to PHYSO, the stronger their correlation, suggesting that AVP may have been acting as a secretagogue for ACTH. Administered AVP significantly increased the secretion of ACTH in the patients and control subjects to a similar degree, and AVP given after PHYSO did not augment the HPA axis response to a greater degree in the depressives than in the control subjects. Plasma estradiol and testosterone were within the normal range for all four groups of subjects and were not significantly related to their HPA axis hormone responses. The study results support the hypothesis of heightened cholinergic sensitivity in premenopausal female, but not in male, patients with major depression. The low dose of PHYSO used may represent a useful paradigm for central cholinergic stimulation of the HPA axis.     

The power of the visible: the meaning of diagnostic tests in chronic back pain

This article explores the meaning of diagnostic tests for people with chronic back pain. Lower back pain is one of the most common health problems in the US. Five to ten percent of the patients who visit a primary care provider for back pain ultimately develop a chronic condition. We draw on interviews with chronic back pain patients in Atlanta, Dallas and Seattle to argue that testing constitutes an important element in the legitimation of pain for these patients. We discuss three aspects that make testing an area of concern for patients: a strong historical connection between visual images and the medicalization of the interior of the body, a set of cultural assumptions that make seeing into the body central to confirming and normalizing patients' symptoms, and the concreteness of diagnostic images themselves. Our interviews show that when physicians cannot locate the problem or express doubt about the possibility of a solution, patients feel that their pain is disconfirmed. Faced with the disjunction between the cultural model of the visible body and the private experience of pain, patients are alienated not only from individual physicians but from an important aspect of the symbolic world of medicine. This paper concludes by suggesting that a fluid, less localized understanding of pain could provide a greater sense of legitimacy for back pain patients.     

Laparoscopic-assisted colorectal surgery

PURPOSE: To audit the development and outcomes of laparoscopic colorectal surgery at the Royal Brisbane Hospital. METHODS: Since July 1991, laparoscopic-assisted colectomy for benign and malignant colorectal disease has been performed on more than 300 patients at the Royal Brisbane Hospital. This paper summarizes the outcome for the first 240 patients who underwent a laparoscopic colorectal procedure. All laparoscopic data were collected prospectively, and for selected studies, data were compared with open surgical controls. RESULTS: Nineteen patients required open conversion (7.9 percent). There was a significant decrease in wound infection rates in patients having a laparoscopic-assisted colectomy (3.6 percent) compared with historical controls (7.9 percent) (P<0.05; chisquared). There were five anastomotic leaks, five laparotomies for postoperative adhesive obstruction, and four perioperative deaths. A total of 103 patients had a procedure for colorectal cancer. Of the 79 potentially curative procedures, there have been 5 (6.3 percent) recurrences to date. CONCLUSION: The overall morbidity and mortality in this series seem to be acceptable compared with that of open procedures.     

Sensitivity and tolerance to nicotine in smokers and nonsmokers

We studied the responses of smokers and life-long non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n=8), non-smokers on a 30 mg patch (n=8) and smokers on a 30 mg patch (n=8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD=3.7), 10.9 (SD=4.2) and 4.1 (SD=2.7) ng/ml in the three groups, respectively (P<0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch ( C_max 13.9 ng/ml, SD=4.9; T_max 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P<0.01) within the first hour, and seven dropped out (P<0.01) at 3–8 h due mainly to severe nausea, vomiting or headache ( C_max 18.4 ng/ml, SD=4.9; T_max 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour ( C_max 7.9 ng/ml, SD=3.0; T_max 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.