An answered call for aid? Cannabinoid clinical framework for the opioid epidemic.

BACKGROUND: The opioid crisis continues in full force, as physicians and caregivers are desperate for resources to help patients with opioid use and chronic pain disorders find safer and more accessible non-opioid tools. MAIN BODY: The purpose of this article is to review the current state of the opioid epidemic; the shifting picture of cannabinoids; and the research, policy, and current events that make opioid risk reduction an urgent public health challenge. The provided table contains an evidence-based clinical framework for the utilization of cannabinoids to treat patients with chronic pain who are dependent on opioids, seeking alternatives to opioids, and tapering opioids. CONCLUSION: Based on a comprehensive review of the literature and epidemiological evidence to date, cannabinoids stand to be one of the most interesting, safe, and accessible tools available to attenuate the devastation resulting from the misuse and abuse of opioid narcotics. Considering the urgency of the opioid epidemic and broadening of cannabinoid accessibility amidst absent prescribing guidelines, the authors recommend use of this clinical framework in the contexts of both clinical research continuity and patient care.

Complete remission of previously intractable peripheral cutaneous T-cell lymphoma of the lower extremity using isolated hyperthermic limb perfusion with melphalan (1-phenylalanine mustard).

The patient is a 74-year-old woman first diagnosed with a peripheral cutaneous T-cell lymphoma (PCTCL) in April of 1994. Initially she presented with subcutaneous indurated areas in the right forearm, scapula, and submadibular region. After chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), she went into remission for 2 years before relapse of her PCTCL localized to the right lower extremity. Persistent isolated disease in the extremity since then led to numerous chemotherapy regimens and localized radiation therapy. Due to dramatic limb threatening progression of the disease in 2001, she underwent isolated hyperthermic limb perfusion with melphalan (1-phenylalanine mustard). Although limb preservation could not be achieved, this treatment resulted in complete clinical and pathological regression of the lesions of the perfused extremity.

Renal artery stenosis: duplex US after angioplasty and stent placement.

PURPOSE: To evaluate the hemodynamic outcome of technically successful percutaneous transluminal renal artery angioplasty and stent placement (PTRAS) with duplex ultrasonography (US). MATERIALS AND METHODS: Eighteen patients who underwent PTRAS in 22 renal arteries were prospectively examined. All had abnormal preprocedural duplex US findings. Those who had significant renal artery stenosis (>70%) at angiography and underwent technically successful percutaneous interventions were enrolled. Standard intrarenal duplex US parameters (acceleration index [AI], acceleration time, waveform morphology grade, and resistive index) were compared before and after interventions. RESULTS: A significant AI increase occurred after PTRAS (9.02 m/sec(2) +/- 4.85 [SD]), as compared with before intervention (2.34 m/sec(2) +/- 2.03; P <.001). Acceleration time significantly decreased from 0.084 second +/- 0.049 to 0.032 second +/- 0.008 (P <.01). There was also a significant resistive index increase from 0.69 +/- 0.12 to 0.79 +/- 0.12 (P <.01). Abnormal waveform morphology (modified Halpern waveform grade 3-6) was present in 19 (86%) of 22 intrarenal arteries prior to intervention, as compared with one (5%) after PTRAS (P <.001). In the instance in which an abnormal waveform persisted after intervention, waveform morphology improved from grade 6 to grade 3, with a concomitant AI increase from 0.96 to 5.1 m/sec(2). CONCLUSION: The findings suggest an important potential role for duplex US in noninvasive assessment of the immediate hemodynamic outcome and long-term follow-up of PTRAS.

Predicting change in depression following renal transplantation: effect of patient coping preferences.

Improvement in patient quality of life is a central goal of renal transplantation. This study examined the hypothesis that change in depression following transplantation would vary as a function of patient coping preferences. Sixty patients were assessed with the Krantz Health Opinion Survey and the Beck Depression Inventory while on the waiting list for a cadaveric renal transplant. Patients were reassessed approximately 12 months later. Among the 33 patients receiving a transplant during the follow-up period, those with a high preference for health-related information exhibited a substantial reduction in depression. In contrast, patients low in preference for information showed a slight increase in depression. Among the 27 patients who were not transplanted during the follow-up period, preference for information had no effect on depression. Patient differences in preference for behavioral involvement did not exert a significant effect on depression.

Proteinmorphosis: a mechanical model for protein conformational changes.

Proteinmorphosis is a physically-based interactive modeling system for simulating large or small conformational changes of proteins and protein complexes. It takes advantage of the cross-linked one-dimensional nature of protein chains. The user can, based on her chemical knowledge, pull pairs of points (lying either on a single protein or on different molecules) together by specifying geometric distance constraints. The resulting conformation(s) of the molecule(s) of interest is computed by an efficient finite element formalism taking into account elasticity of the protein backbone, van der Waals repulsions, hydrogen bonds, salt bridges and the imposed distance constraints. The conformational change is computed incrementally and the result can be visualized as an animation; complete interactivity is provided to position and view the proteins as desired by the user. Physical properties of regions on the protein can also be chosen interactively. The conformational change of calmodulin upon peptide binding is examined as a first experiment. It is found that the result is satisfactory in reproducing the conformational change that follows on peptide binding. We use Proteinmorphosis to study the cooperative hemoglobin oxygen binding mechanism in a second, more sophisticated, experiment. Different modeling strategies are designed to understand the allosteric (cooperative) binding process in this system and the results are found to be consistent with existing hypotheses.

Cynical hostility, powerful others control expectancies, and patient adherence in hemodialysis.

OBJECTIVE: The present study examined the joint role of cynical hostility and powerful others health locus of control expectancies in predicting regimen adherence in a sample of center hemodialysis patients. METHOD: Forty-eight hemodialysis patients completed the Cook-Medley Hostility (Ho) Scale and the Powerful Others Health Locus of Control (PHLC) scale. Adherence to the fluid-restriction and phosphorus reduction components of the treatment regimen was assessed by examining patients' interdialysis session weight gains and serum phosphorus (P) levels. RESULTS: In a hierarchical regression analysis, higher hostility was associated with significantly higher serum P levels indicating poorer dietary and medication adherence. The main effect for hostility was qualified by the interaction of hostility and PHLC. This pattern indicated that the deleterious effect of hostility on adherence was most pronounced among patients possessing the expectancy that positive health outcomes are not strongly contingent on the actions or advice of powerful others (eg. health care providers). Similar analyses failed to show significant effects for hostility or PHLC in the prediction of interdialytic weight gain. CONCLUSIONS: The present findings suggest that jointly assessing hostility and health-related expectancies may be useful in identifying chronically ill patients who are potentially at risk for difficulties in performing a prescribed regimen.

Monitoring attentional style and medical regimen adherence in hemodialysis patients.

Previous research involving individuals facing chronic health problems suggests that an attentional style characterized by pronounced monitoring of threat-relevant information is associated with poorer behavioral and emotional adjustment. This study examined the hypothesis that a pronounced monitoring style would be associated with poorer medical regimen adherence in a sample of 51 chronic hemodialysis patients. Hierarchical regression analyses (controlling for demographic factors and trait anxiety) revealed that "high monitors" exhibited higher interdialysis weight gains and higher serum K values reflecting poorer adherence to fluid-intake and dietary restrictions. However, monitoring was not associated with a measure of medication adherence. Partial support was found for a model suggesting that a lack of perceived control is responsible for the relationship between higher monitoring and poorer adherence.

Social support and conscientiousness in hemodialysis adherence.

Previous conclusions regarding the role of social support in hemodialysis adherence are inconsistent, suggesting that other factors may moderate this relationship. Using the Five-Factor Model of Personality, we examined the hypothesis that conscientiousness would interact with social support in predicting fluid-intake and medication adherence in a sample of 56 chronic hemodialysis patients. Hierarchical regression analyses (controlling for demographic, clinical, and other personality variables) revealed a significant interaction between social support and conscientiousness. However, inconsistent with prediction, high support among patients with low conscientiousness was associated with poorer fluid-intake adherence, while support had little effect on fluid-intake adherence among high conscientiousness patients. No main or interactive effects were found for support or conscientiousness on a measure of medication adherence.

Body consciousness, illness-related impairment, and patient adherence in hemodialysis.

Recent theory and evidence suggests that bodily self-focusing tendencies (e.g. private body consciousness) may be associated with medical regimen adherence among chronically ill patients. The present study examined the joint effects of private body consciousness and degree of illness-related physical impairment on treatment regimen adherence in a sample of 52 hemodialysis patients. It was predicted that the effect of PBC on adherence would vary as a function of patients' level of illness-related physical impairment. For patients experiencing more severe impairment, higher PBC scores were associated with poorer adherence to the prescribed medication and dietary regimen. In contrast, for patients experiencing a relatively low degree of disease-related physical impairment, higher private body consciousness was associated with more favorable adherence. Results are discussed in terms of self-focused attention and behavioral self-regulation theories. Implications for future research and clinical intervention are also discussed.

Coping with treatment-related stress: effects on patient adherence in hemodialysis.

With a modified version of the Ways of Coping Checklist, the relation of coping to adherence among 57 hemodialysis patients was examined. The association of a particular type of coping to adherence was predicted to depend on the specific type of stressful encounter being considered. As predicted, coping efforts involving planful problem solving were associated with more favorable adherence when used in response to stressors involving a relatively controllable aspect of the hemodialysis context. For less controllable stressors, coping efforts involving emotional self-control were associated with more favorable adherence. The seeking of informational support in response to an uncontrollable encounter was associated with poorer fluid-intake adherence. Confrontive coping was associated with poorer adherence for both high- and low-control situations.

Takayasu's arteritis associated with Wiskott-Aldrich syndrome.

A unique case of a Chinese boy with Wiskott-Aldrich syndrome (WAS) associated with Takayasu's arteritis is reported. He had eczema, epistaxis and recurrent infections since early infancy and was found to have thrombocytopenia, negative delayed-type skin hypersensitivity, low T cell number and impaired lymphocyte proliferation to phytohaemagglutinin and concanavalin A. He had high normal serum immunoglobulin (Ig)G and IgA with low IgM and isohaemagglutinin. He presented with hypertensive encephalopathy at 5.5 years of age and an aortogram demonstrated abdominal aortic aneurysm with bilateral stenosis of renal arteries resulting in renovascular hypertension. His hypertension was difficult to control medically and autotransplant of his kidneys to the iliac arteries was performed, but he died in the immediate postoperative period. The relationship between immunodeficiency and collagen-vascular disease was discussed.

Multidimensional chirp algorithms for computing Fourier transforms.

Continuous versions of the multidimensional chirp algorithms compute the function G(y)=F(My), where F(y) is the Fourier transform of a function f(x) of a vector variable x and M is an invertible matrix. Discrete versions of the algorithms compute values of F over the lattice L(2)=ML(1 ) from values of f over a lattice L(1), where L(2) need not contain the lattice reciprocal to L(1). If M is symmetric, the algorithms are multidimensional versions of the Bluestein chirp algorithm, which employs two pointwise multiplication operations (PMOs) and one convolution operation (CO). The discrete version may be efficiently implemented using fast algorithms to compute the convolutions. If M is not symmetric, three modifications are required. First, the Fourier transform is factored as the product of two Fresnel transforms. Second, the matrix M is factored as M=AB, where A and B are symmetric matrices. Third, the Fresnel transforms are modified by the matrices A and B and each modified transform is factored into a product of two PMOs and one CO.

Effect of dietary potassium on blood pressure, renal function, muscle sympathetic nerve activity, and forearm vascular resistance and flow in normotensive and borderline hypertensive humans.

We evaluated the effect of a low potassium diet on blood pressure in normotensive (NT) and in borderline hypertensive subjects (BHT). There were 11 BHT men (age, 24.6 +/- 1.2 years) and 10 NT men (age, 23.5 +/- 1.0 years). Subjects were studied while on both low potassium, high sodium (30 meq/day, 400 meq/day) diets and high potassium, high sodium (100 meq/day, 400 meq/day) diets, each taken for 6 days. During the low potassium diet, daytime ambulatory systolic blood pressure increased in both NT (123 +/- 5 mm Hg, low potassium, vs. 116 +/- 4 mm Hg, high potassium, p less than 0.01) and BHT groups (134 +/- 3, low potassium, vs. 124 +/- 3, high potassium, p less than 0.001). Mean blood pressure was not different in NT during the two diets but was significantly higher during the low potassium diet in BHT subjects (97 +/- 2 mm Hg low potassium, vs. 92 +/- 1 mm Hg, high potassium, p less than 0.05) without change in heart rate in BHT subjects during the two diets. Low potassium diet increased the postural rise in diastolic blood pressure when subjects changed from the supine position to quiet standing (standing diastolic blood pressure for NT: low potassium, 79 +/- 2 mm Hg vs. high potassium, 72 +/- 2 mm Hg; for BHT: low potassium, 89 +/- 2 mm Hg vs. high potassium diet, 83 +/- 2 mm Hg, p less than 0.01). The effects of low potassium diet on blood pressure were not related to marked changes in renal hemodynamics, in plasma renin activity, in aldosterone, or in norepinephrine, nor to increases in forearm vascular resistance or in muscle sympathetic nerve activity. In fact, muscle sympathetic nerve activity decreased in the BHT group during low potassium compared with high potassium diets (p less than 0.001) and did not change in the NT group. Sympathetic nerve activity was also higher in BHT compared with the NT group during high potassium and low potassium diets, p less than 0.001. In the NT group, the low potassium diet was associated with lower hematocrit levels, weight gain, and increased 24 hour urinary calcium levels. After the low potassium diet, serum potassium fell in both groups, and serum phosphorus fell significantly in the BHT group.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal and hemodynamic effects of atrial natriuretic peptide in patients with cirrhosis.

The effects of anaritide, a 25-amino-acid synthetic analogue of ANP, were evaluated in 28 patients with cirrhosis complicated by ascites and/or edema. Each patient received two doses of the agent, as well as an infusion of placebo. Six different doses were tested ranging from 0.015-0.300 microgram/kg/min. The infusions lasted for 2 hours and were flanked by both baseline and recovery periods. There was a significant effect of placebo on urinary sodium and chloride excretion rates but no effect on urine flow rate. In response to anaritide, the urine flow rate increased at 0.03, 0.06, 0.075, and 0.100 microgram/kg/min. The sodium and chloride excretion rates increased at all doses except the highest dose. There was no definite effect of anaritide on urinary potassium, calcium, and phosphate excretion rates. There was also no significant effect on creatinine clearance. The mean arterial pressure decreased in response to the 0.060, 0.075, and 0.100 microgram/kg/min doses. In addition, five of the patients receiving the highest dose (0.300 microgram/kg/min) had decreases in their systolic pressures to 90 mm Hg or less. In conclusion, anaritide is natriuretic and diuretic in patients with cirrhosis complicated by ascites and/or edema. Its effect, however, on arterial pressure may limit its therapeutic potential in this patient population.

Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings.

Reports of elevated plasma catecholamine levels and augmented responses to autonomic blockade suggest increased sympathetic tone in borderline hypertension. It is not known if this reflects greater sympathetic neural outflow. We directly recorded muscle sympathetic nerve activity (microneurography) in 15 normotensive and 12 borderline hypertensive age-matched men to determine whether borderline hypertensive individuals have elevated sympathetic nerve activity. Supine heart rate, blood pressure, plasma norepinephrine, and efferent muscle sympathetic nerve activity (peroneal nerve) were measured after 6 days of both low and high dietary sodium intake (10 and 400 meq sodium/24 hr). Sympathetic nerve activity was elevated significantly in borderline hypertensive individuals on both low (37 +/- 1 in borderline hypertensive individuals vs. 29 +/- 1 bursts/min in normotensive individuals; p less than 0.01) and high (25 + 1 in borderline hypertensive individuals vs. 16 +/- 1 bursts/min in normotensive individuals; p less than 0.01) sodium diets. The borderline hypertensive group had higher systolic (p less than 0.01) and diastolic (p less than 0.05) blood pressures independent of sodium intake. Across both groups, high sodium intake reduced muscle sympathetic nerve activity (p less than 0.001), plasma norepinephrine (p less than 0.001), diastolic blood pressure (p less than 0.02), heart rate (p less than 0.002), and increased weight (p less than 0.005). A significant (p less than 0.05) group-by-diet interaction was observed for plasma norepinephrine levels. Specifically, compared with the normotensive group, plasma norepinephrine levels in the borderline hypertensive group tended to be higher on low sodium diet (p = 0.08) and lower on high sodium diet (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of four-week treatment with oxitropium bromide on lung mucociliary clearance in patients with chronic bronchitis or asthma.

The effect of oxitropium bromide on lung mucociliary clearance, pulmonary function and viscoelastic properties of sputum was investigated in 10 asthmatics and 10 chronic bronchitics. A controlled, double-blind, crossover study was performed. Following a baseline (B) measurement the patients were, in a random order, allocated placebo (P) or oxitropium bromide (O; 0.1 mg/puff), administered from metered dose inhalers, which they used for 4 weeks at a dose of 2 puffs t.d.s. This test medication was used in conjunction with their normal medication. At the end of the treatment period the patients were assessed, the treatments were then crossed over and a final assessment made 4 weeks later. The administration of oxitropium bromide resulted in (1) small but statistically significant increases in pulmonary function (less than 10% vs. placebo); (2) increased penetrance of radioaerosol into the lungs (mean +/- SEM alveolar deposition: 35 +/- 3, 26 +/- 3 and 24 +/- 3% for the O, P and B runs respectively; p less than 0.025); (3) no significant change in particle clearance rate from the lungs despite their deeper penetration (mean +/- SEM area under the tracheobronchial clearance curves between 0 and 6 h: 317 +/- 26, 324 +/- 25 and 287 +/- 25%.h for the O, P and B runs respectively; p greater than 0.1); (4) no alteration in sputum production, and (5) no significant changes in apparent viscosity (mean +/- SEM: 640 +/- 162, 446 +/- 79 and 557 +/- 115 mPa.s for the O, P and B runs, respectively; p greater than 0.1) and elasticity (mean +/- SEM: 3,682 +/- 1,383, 1,779 +/- 353 and 2,061 +/- 366 mPa for the O, P and B runs, respectively; p greater than 0.1) of sputum. When the two groups, i.e. the chronic bronchitics and asthmatics, were studied separately, no significant differences in any parameter measured (other than radioaerosol penetrance which was significantly enhanced on oxitropium bromide in chronic bronchitics) were noted between the three assessments.

Dietary salt produces abnormal renal vasoconstrictor responses to upright posture in borderline hypertensive subjects.

We studied the effect of high and low NaCl diets in normotensive and borderline hypertensive subjects to determine if a high NaCl diet produces abnormal renal vasoconstriction during the stress of upright posture in borderline hypertensive subjects. We studied 13 normotensive young men with diastolic blood pressures below 85 mm Hg and nine borderline hypertensive young men defined by diastolic blood pressures intermittently above 90 mm Hg. The subjects achieved comparable sodium balance during 6 days of low NaCl (10 mEq Na, 40 mEq Cl, 100 mEq K) and high NaCl (400 mEq Na, 400 mEq Cl, 100 mEq K) diets. In the normotensive subjects, standing for 30 minutes resulted in a tendency for diastolic blood pressure to fall during both diets. In contrast, during standing borderline hypertensive subjects showed no change in diastolic blood pressure during the low salt diet and a tendency for diastolic blood pressure to increase after the high salt diet. Standing reduced renal plasma flow in both groups during both diets. However, only during the high NaCl diet did the absolute decrease and percent decrease in renal plasma flow during standing differ significantly (p less than 0.05 and p less than 0.01, respectively) between the borderline hypertensive (-151 +/- 24 ml/min/1.73m2; -29 +/- 4%) and normotensive subjects (-79 +/- 17 ml/min/1.73m2; -15 +/- 3%). The resultant increase in the renal vascular resistance index with standing did not differ between the two groups during the low NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)