Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: a randomized controlled trial

CONTEXT: Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies. OBJECTIVE: To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy. DESIGN: Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997. SETTING: Outpatient clinics at 20 sites. PATIENTS: The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale. INTERVENTION: Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo. MAIN OUTCOME MEASURES: The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results. RESULTS: Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06). CONCLUSION: Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.     

Forefoot deformity, pain, and mobility in rheumatoid and nonarthritic subjects

OBJECTIVE: To evaluate how painful metatarsal arthritis affects foot and ankle mechanics and mobility. METHODS: We studied 16 symptomatic forefeet in 10 patients with rheumatoid arthritis (RA) and compared them with 14 asymptomatic forefeet in 7 nonarthritic subjects. RA limbs with significant disease at other locations were excluded. We measured pain and deformity of the foot using a visual analog scale and a modified articular index. A video based 3 dimensional gait analysis system and force platform were used to collect data on subjects walking barefoot at a self-selected pace according to an established protocol. Mobility level was quantified using the Sickness Impact Profile (SIP) ambulation subscale. RESULTS: We observed considerable pain and deformity of the forefeet of RA subjects. During gait, motion and force measures revealed that RA subjects significantly (p < 0.005) delayed and reduced forefoot loading, which minimized use of the foot as a rigid level for push off. As a result, stride lengths were shorter and gait was slower compared to nonarthritic subjects. SIP scores revealed that these changes in gait resulted in moderate disability in RA subjects (p=0.05). CONCLUSION: Impairments of the forefoot due to RA include pain and deformity, which produce characteristic stance phase abnormalities in foot function, a slow walking speed, and moderate disability.     

Evidence that acetyl-CoA carboxylase isoforms play different biological roles in H9c2 cardiomyocyte

Twelve patients with cervical dystonia (CD) and predominant rotation were studied to determine the effects of changes in head posture on the specific patterns of cervical muscle activity. Turns analysis was used to quantify muscle activity underlying head rotation, recorded simultaneously from the agonist and antagonist muscle pairs bilaterally (sternocleidomastoid [SCM] and splenius [SPL]). Muscle activity was compared between the uncompensated dystonic posture and during the maintenance of midposition. In addition, patients were separated into two groups (geste = 6; no geste = 6) based on whether they had a clinically efficacious geste to determine the effect of geste on patterns of cervical muscle activity. Muscle activity was measured during the maintenance of midposition with and without a clinical or simulated geste. Differences in muscle activity between the groups and postures were compared using repeated measure analysis of variance (ANOVA) analyses. The four muscles tested showed a significant difference in muscle activity in the uncompensated dystonic posture as a result of the increased activity in the agonist muscle pair (SCM and SPL responsible for the dystonic posture) (EMG amplitude: F[1,11] = 18.81, p = 0.0012; EMG frequency: F[1,11] = 32.07, p = 0.0001). Maintaining the head in the midposition was associated with a significant reduction in muscle activity compared with the uncompensated dystonic posture (EMG amplitude: F[1,9] = 6.36, p < 0.033; EMG frequency: F[1,9] = 10.96, p < 0.0091). This reduction in midposition muscle activity was significantly greater in the agonist muscle pair (EMG amplitude: F[1,10] = 19.70, p = 0.0013; EMG frequency: F[1,10] = 44.67, p < 0.0001). In the patients with clinically effective geste, there was no additional reduction in muscle activity observed in the midposition when they performed their geste (EMG amplitude: F[1,9] = 4.63, p = 0.060; EMG frequency: F[1,9] = 1.22, p = 0.298). These findings suggest that CD with rotation is characterized by predominantly increased agonist muscle activation. Patients with CD retain the ability to modulate this involuntary agonist muscle activity to maintain the head in the midposition. The maintenance of the midposition does not seem to be facilitated by geste.     

Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy

BACKGROUND: Conventional treatment for painful peripheral diabetic neuropathy is largely symptomatic and often ineffective, with unacceptable side-effects. We tested electrical spinal-cord stimulation for the management of chronic neuropathic pain. METHODS: Ten diabetic patients who did not respond to conventional treatment (mean age 51 [SD 9.3] years, six with type II diabetes, mean duration of diabetes 12 [6.3] years, mean duration of neuropathy 5 [2.1] years) were studied. The electrode was implanted in the thoracic/lumbar epidural space. Immediate neuropathic pain relief was assessed by visual analogue scale (VAS) after connecting the electrode, in a random order, to a percutaneous electrical stimulator or to a placebo stimulator. Exercise tolerance was assessed on a treadmill. FINDINGS: Eight subjects had statistically significant pain relief with the electrical stimulator (p < 0.02) and were therefore converted to a permanent system. Statistically significant relief of both background and peak neuropathic pain was achieved at 3 months (n = 7, p = 0.016), at 6 months (n = 7, p = 0.03), and at the end of the study (14 months, n = 7, background pain p = 0.06, peak pain p = 0.03). One patient died 2 months after the start of the study of unrelated cause while continuing to benefit from treatment and another patient ceased to benefit at 4 months. McGill pain questionnaire scores with the stimulator turned off did not change significantly from baseline scores, indicating that the severity of the underlying pain was unaltered. However, with the stimulator turned on, there was a statistically significant (p < 0.05) improvement in all four components of the score, by the end of the study. At the end of the study, six patients continued to gain significant pain relief and used the stimulator as the sole treatment for their neuropathic pain. For example, median background and peak pain scores at the end of study, were, respectively, 77 and 81 with the stimulator off and 23 and 20 with the stimulator on. Exercise tolerance significantly improved at 3 months (n = 7, median % increase 85 [IQR, 62-360], p = 0.015) and at 6 months (n = 6, 163 [61-425], p = 0.0007). Electrophysiological tests, vibration perception-threshold, and glycaemic control were unchanged. INTERPRETATION: Electrical spinal-cord stimulation offers a new and effective way of relieving chronic diabetic neuropathic pain and improves exercise tolerance. The technique should be considered in patients with neuropathic pain who do not respond to conventional treatment.     

Performance of a self-administered mailed version of the Quality of Well-Being (QWB-SA) questionnaire among older adults

OBJECTIVES: The Quality of Well-Being questionnaire is a measure of health-related quality of life (HRQoL) that has several desirable properties. Its widespread use has been hindered because it is difficult to administer. To overcome this limitation, a new self-administered form has recently been developed. This study examined the feasibility of using the Quality of Well-Being-Self-Administered (QWB-SA) questionnaire in an older population. METHODS: The Quality of Well-Being-Self-Administered questionnaire was sent to 430 community-dwelling individuals aged 65 years and older who were randomly selected from primary care physicians' offices. Response patterns, scaling distributions, and the acceptability of the survey were examined for all respondents. The results of the QWB-SA questionnaire were compared to the Sickness Impact Profile (SIP) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) for those individuals who also had completed the latter two surveys approximately 10 months earlier and whose health had not changed substantially in the meantime. RESULTS: Three hundred and one older adults (70%) responded. The mean QWB-SA questionnaire score was 0.7035. The scores were not skewed, and there were no floor or ceiling effects. The mean time to complete the QWB-SA questionnaire was 14.2 minutes, which was significantly shorter than for the SIP (19.3 minutes) but significantly longer than for the SF-36 (12.5 minutes). Subjects rated their satisfaction with the QWB-SA questionnaire somewhat lower than for the SIP and similar to SF-36. Correlations between the QWB-SA questionnaire and the SIP and SF-36 were moderate and were generally stronger for measures of physical health than for other domains such as mental health. CONCLUSIONS: The self-administered QWB questionnaire was acceptable to older respondents, and it correlated with other measures of health-related quality of life. It can be considered as a candidate for some research applications among older adults.     

Who suffers most from leg ulceration?

This study examines health-related quality of life (HRQoL) in patients with leg ulceration and determines which patient groups are affected most by this condition. A cross-sectional study using the Nottingham Health Profile (NHP) and age/sex-matched normal scores in patients entering six clinical audit cycles was carried out. The 758 patients included in the study (mean age 74.6 years, 64% women) had been affected by leg ulceration for a median of 10.5 months (range 0.5 to 708). Patients produced significantly higher scores than age/sex-matched normal values for all domains of the NHP, indicating poorer HRQoL (all p < 0.001). Increasing age led to greater deficits in energy (p < 0.001) and mobility (p < 0.001) with greater social isolation (p = 0.044). Women experienced poorer energy, sleep patterns, mobility and emotional reactions (all p < 0.001), and increased physical pain and social isolation (p < 0.05) compared to men. However, higher scores may be expected for older women based on age/sex-matched normal values. After adjustment for age/sex-matched normal values, it was the younger patients who experienced a greater deficit in HRQoL over all domains of the NHP, with men scoring higher than women in the domains of bodily pain, sleep and social isolation (p < 0.001) and energy (p = 0.015). Leg ulceration has a major impact on patients' HRQoL as detected by the NHP. The excess in scores compared with age/sex-matched normal values indicate that it is younger male patients in whom ulceration makes a greater impact on HRQoL.     

Musculoskeletal complaints and fibromyalgia in patients attending a respiratory sleep disorders clinic

OBJECTIVE: To determine the frequency of fibromyalgia (FM) syndrome and reporting of pain in an unselected group of patients attending a respiratory sleep disorders clinic, and to examine the association of physical activity and levels of reported pain. METHODS: 108 consecutive patients attending a respiratory sleep disorders clinic were interviewed and examined, blind to sleep disorder status. Assessment of musculoskeletal pain symptoms included patient history of pain, painful sites marked on a mannequin, visual analog scale (VAS) pain score, and tender point count. Daily physical activity was recorded, and all patients underwent nocturnal polysomnography, blind to clinical status. RESULTS: FM was identified in 3 patients (2.7%). Pain reporting was more strongly associated with reduced physical activity than with a specific sleep disorder. Patients with reduced physical activity were more likely to have pain symptoms than physically active patients: tender point count > or = 6 (p = 0.002), > or = 3 sites marked on mannequin (p = 0.008), axial pain (p = 0.003), and VAS pain score (p = 0.008). CONCLUSION: FM by defined criteria was uncommon in patients with a primary complaint of disturbed sleep, and in particular, patients with sleep apnea. Reduced physical activity was strongly associated with reported pain symptoms.     

A study on menopausal symptoms and health needs among middle aged women

During the middle age of a woman's life cycle, several health changes and problems occur. Therefore, middle aged women must manage their health and maintain quality life by coping with bodily changes. However, today there is not enough research and health programs for middle aged women. Data from the study will be used for health promotion program development of middle aged women. Data was collected from January 21 to 24, 1995 by telephone interview. Four hundred middle aged women between 40 and 59 years old and living in Chon Ju City were interviewed. The results of this study were as follow: 1. Frequency rate of menopausal symptoms was 38.4%. The most serious menopausal symptom was psychosomatic symptom. Mean score orders of experienced symptoms were back pain, joint pain (1.80), nervousness (1.80), general weakness (1.67). 2. The most important problems as perceived by the clients were children (45.8%), health (24.0%) and economics (7.8%). The most serious health problems were concerning the muscle-skeletal system (45%) such as arthritis, spinal disk problems and osteoporosis. Adult diseases (14.5%) such as hypertension and diabetes were also health concerns. Health management activities reported were exercise (22.5%), social activity (12%) and inactivity (53%). 33% of clients were interested in health groups and they wanted a program of health education, exercise and social activity to be provided. 3. General characteristic variables were significantly related to the level of menopausal symptoms as follows: age (t = -2.06, p = 0.040), status of marriage (t = -3.56, p = 0.000), educational level (F = 4.35, p = 0.05) and menopausal status (t = 4.37, p = 0.000).     

Survival and predictors of disability in Turkish MS patients. Turkish Multiple Sclerosis Study Group (TUMSSG)

OBJECTIVE: To examine the natural history, survival, and prognostic factors in a sample of Turkish MS patients. METHOD: This multicenter study included 1,259 definite MS patients diagnosed according to the criteria of Poser et al. Actuarial analysis of selected disability levels of 3, 6, 8, and 10 achieved with the Expanded Disability Status Scale (EDSS); a multivariate Cox regression analysis for prognostic factors related to time to reach EDSS > or = 6; and Pearson's correlation coefficient for individual factors were performed. RESULTS: The survival (+/- SE) at 15 years from onset was 94.6 +/- 2.9%, and at 25 years was 89.0 +/- 5.8%. The disability reached by 15 years was EDSS > or = 3 in 66.4%, EDSS > or = 6 in 41.2%, EDSS > or = 8 in 10.5%, and EDSS = 10 in 5.4%. The most significant unfavorable prognostic factors were progressive course (relative risk [RR], 3.73; CI, 2.71 to 5.13) and sphincter symptoms at onset (RR, 1.86; CI, 1.23 to 2.82), followed by male sex, motor symptoms at onset, and a high attack frequency within the first 5 years. Primary progressive disease was correlated positively with male sex (r = 0.0895, p = 0.001), older age (r = 0.1807, p = 0.000), and motor (r = 0.1433, p = 0.000) or sphincter symptoms (r = 0.1001, p = 0.000) at onset, unlike relapsing-remitting and secondary progressive disease. CONCLUSIONS: Although a slightly better prognosis is observed in the Turkish MS population, early prognostic factors are similar to most of the previous Western series. Primary progressive disease, mostly seen in older men with motor and sphincter involvement at onset, has a worse prognosis and may represent a distinct behavioral variant of MS.     

Patterns of symptoms in functional dyspepsia: role of Helicobacter pylori infection and delayed gastric emptying

OBJECTIVE: Functional dyspepsia (FD) is a syndrome in which several causes are probably involved. Our aim was to investigate the association between specific dyspeptic symptoms and Helicobacter pylori infection or delayed gastric emptying. METHODS: Nine hundred thirty-five consecutive outpatients with unexplained dyspepsia were studied. After appropriate investigation, 304 patients were diagnosed as affected by chronic FD and were tested for H. pylori infection and gastric emptying of solids by means of 13C-urea and 13C-octanoic acid breath tests. Four dyspeptic symptoms (epigastric pain or burning, postprandial fullness, nausea, and vomiting) were scored as absent, mild, moderate, or severe (0-3) according to their influence on the patients' activities. Symptoms of irritable bowel syndrome and gastroesophageal reflux disease were also assessed. On the basis of symptom scores, three groups were identified: "prevalent pain" (10.5%), "prevalent discomfort" (32.6 %), and "unclassifiable" dyspepsia (56.9%). RESULTS: Of the 304 patients with FD, 208 (68.4 %) were H. pylori-positive on urea breath test. Gastric emptying was delayed in 99 subjects (32.6%). Patients with "prevalent pain" were infected significantly more often (81.2% vs 59.6%; p = 0.026) and less frequently had delayed gastric emptying (6.2% vs 40.4%; p = 0.0001) than those with "prevalent discomfort." H. pylori infection was independently associated with age > or =40 yr and epigastric pain or burning > or =2 (odds ratio [OR] and 95% confidence interval [CI] 4.09 [2.39-7.00] and 1.70 [1.04-2.77], respectively). Delayed gastric emptying was independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (OR [95% CI]: 3.13 [1.06-9.18]). H. pylori status had no influence on gastric emptying. Logistic regression analysis showed that delayed gastric emptying, female sex, and concomitant symptoms of inflammatory bowel syndrome were independently associated with a cumulative score > or =6 for postprandial fullness, nausea, and vomiting (p = 0.0281, p = 0.0387, and p = 0.0316, respectively). Moreover, concomitant symptoms of gastroesophageal reflux disease, female sex, and H. pylori infection were independently associated with epigastric pain or burning > or =2 (p = 0.002, p = 0.0001, and p = 0.0875, respectively). CONCLUSIONS: Two subsets of FD patients have been identified on the basis of symptoms. One subgroup is mainly characterized by "prevalent pain," H. pylori infection, and normal gastric emptying; the other one demonstrates "prevalent discomfort" and delayed gastric emptying. These findings shed some light on possible etiopathogenetic mechanisms of FD.     

Evaluation of the RFIPC, a disease-specific health-related quality of life questionnaire, in Swedish patients with ulcerative colitis

BACKGROUND: We wanted to characterize a Swedish version of the Rating Form of Inflammatory Bowel Disease Patient Concerns (RFIPC) with regard to validity, reliability, and responsiveness. METHODS: Two hundred and three consecutive patients with ulcerative colitis were studied. Health-related quality of life (HRQOL) was measured with the disease-specific questionnaire, the RFIPC, and a general questionnaire, the Sickness Impact Profile (SIP). Concerns about general well-being were also reported. Disease activity was measured by means of symptom cards, laboratory tests, and two clinical indices for disease activity. RESULTS: Test-retest reliability using Spearman's r (rs) was 0.79, and internal consistency measured with Cronbach's alpha was 0.95. RFIPC had a fair correlation with concerns about general well-being (rs = 0.69, P < 0.001). There was also a stronger correlation with another measure of HRQOL, the overall SIP score (rs = 0.43), than with measures of disease activity such as stool frequency (rs = 0.28) and sigmoidoscopic grading (NS). The group of patients in relapse had a higher RFIPC sum score than patients in remission (P = 0.001). Measures of HRQOL had a low correlation with disease activity and did not respond to changes in disease activity. CONCLUSION: The Swedish version of the RFIPC is a valid and reliable measure of HRQOL. The SIP and the RFIPC have a good discriminative ability between groups of patients in remission and in relapse. However, they do not seem to be useful in predicting the disease activity or change in disease activity over time in the individual patient.     

Isokinetic strength training of the hemiparetic knee: effects on function and spasticity

PURPOSE: To determine whether isokinetic training can improve the strength of the hemiparetic knee musculature, functional mobility, and physical activity and to evaluate its effect on spasticity in long-term stroke survivors. DESIGN: Nonrandomized self-controlled trial. SUBJECTS: A volunteer sample of 15 community-dwelling stroke survivors of at least 6 months. INTERVENTION: A 6-week (3 days/week, 40 minutes/day) program consisting of warm-up, stretches, reciprocal knee extension and flexion isokinetic strengthening, and cool-down for the paretic limb. MAIN OUTCOME MEASURES: Peak isokinetic hamstring and quadriceps torque, quadriceps spasticity, gait velocity, timed Up and Go, timed stair climb, and the Human Activity Profile (HAP) scores were recorded at baseline, after training, and 4 weeks after training cessation (follow-up). RESULTS: Paretic muscle strength improved after training (p < .05) while tone remained consistent (p > .87). Gait velocity increased after training (p < .05) and at follow-up (p < .05). Changes in stair climbing and timed Up and Go were not significant (p > .37; p > .91), although subjects perceived gains in their physical abilities at follow-up (p < .01). CONCLUSIONS: Gains in strength and gait velocity without concomitant increases in muscle tone are possible after a short-term strengthening program for stroke survivors. The psychological benefit associated with physical activity is significant.     

Assessing health-related quality of life in chronic hepatitis C using the Sickness Impact Profile

In a randomized, controlled trial that demonstrated the efficacy of interferon alfa-2b 3 million units three times a week for 24 weeks in controlling chronic hepatitic C (non-A, non-B), the Sickness Impact Profile (SIP) was used to evaluate the impact of disease and treatment on health-related quality of life (HRQOL). The SIP was self-administered by 160 patients before treatment, at the end of treatment, and at the study endpoint. Before treatment, patients with chronic hepatitis C scored significantly (P < 0.05) higher (worse) than an historical control group of the general population in mean total SIP score and in all categories except eating. The highest degree of impairment was observed in the work, sleep and rest, and recreation and pastimes categories. After treatment, patients who received interferon alfa-2b had significant (P < or = 0.05) improvement in work, sleep and rest, and recreation and pastimes scores. Numerical improvement was observed in total score, physical and psychosocial dimension scores, and most individual category scores. Mean SIP scores were unchanged or slightly worsened in untreated control patients. In responders (patients with improvement in serum alanine aminotransferase levels), the largest improvement was seen in work scores. The SIP appears to be a reliable and valid instrument for describing the impact of chronic hepatitis C on HRQOL but lacks disease-specificity and the ability to reflect clinically relevant changes. Thus the SIP is not the best instrument to evaluate the HRQOL effects of treatment with interferon alfa-2b in patients with chronic hepatitis C.     

Intraoral non-Hodgkin''s lymphoma in seven patients with acquired immunodeficiency syndrome

Transcranial Doppler sonography (TCD) of the middle, anterior and posterior cerebral arteries and of the basilar artery was used to evaluate the mean blood velocity (V mean) and the pulsatility index [PI = (V systolic-V diastolic)/V mean] as a vascular resistance index in 63 patients (male 40, female 23, mean age 43 +/- 19 y) with bacterial meningitis (n = 33, including 2 patients with fungal meningitis) and viral meningitis (n = 30) within 12 h after admission of the patients. The findings were similar for all intracranial arteries. Compared with reference values of 69 healthy volunteers [V mean of middle cerebral artery [MCA] 57 +/- 13 cm/s, MCA-PI 0.83 +/- 0.15], MCA-V mean was increased in patients with Glasgow coma scale (GCS) scores of 14 and 15 (71 +/- 18 cm/s; t-test: p < 0.001), not significantly different in the patients with GCS scores of 10-13 (55 +/- 21 cm/s) and decreased in those with GCS scores of 3-9 (42 +/- 21 cm/s, p < 0.01). The MCA-PI increased from 0.93 +/- 0.22 in the patients with GCS scores of 14-15 to 2.81 +/- 2.06 in those with GCS scores of 3-9 (p < 0.001 vs. controls). By regression analysis, MCA-V mean decreased and MCA-PI increased with decreasing GCS scores (p < 0.001). Only in patients with bacterial meningitis was the Glasgow outcome scale (GOS) score lower the more the MCA-PI was increased (regression analysis p < 0.001). We conclude that in patients with bacterial and viral meningitis, and in a good clinical state, the cerebral blood flow seems increased by hyperemia; with clinical deterioration the cerebral haemodynamics worsen. However, the early assessment of the cerebral blood flow by TCD seems useful for predicting outcome in bacterial meningitis only.     

Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers

BACKGROUND: Circannual variations occur in several serotonergic parameters, including platelet serotonin uptake and platelet [3H]imipramine binding. METHODS: Binding of [3H]lysergic acid diethylamide ([3H]LSD) to platelet serotonin (5-HT)2A receptors and binding of [3H]paroxetine to platelet serotonin uptake sites were studied longitudinally for 1 year in 12 healthy volunteers. RESULTS: For [3H]LSD, the number of binding sites (Bmax) showed no significant seasonal variation (two-way analysis of variance), although Bmax was significantly higher during the months October through February than during the months April through August (32.6 vs. 29.8 fmol/mg protein; p = .015). For [3H]paroxetine, Bmax showed a significant seasonal variation (p = .003) with maximum in August (1322 fmol/mg protein) and minimum in February (1168 fmol/mg protein). The affinity constant (Kd) showed a significant seasonal variation for [3H]LSD binding (p = .046), but not for [3H]paroxetine binding. The seasonal fluctuations in [3H]LSD binding and in paroxetine binding tended to be inversely correlated for Bmax (r = -.70; p = .08) and were significantly negatively correlated for Kd (r = -.88; p = .009). CONCLUSIONS: The present study demonstrates a seasonal effect on platelet serotonin uptake site binding and indicates a possible seasonal effect on 5-HT2A receptor binding. The results imply that circannual fluctuations should be taken into account when these platelet serotonin markers are studied.     

Microanalysis of adolescent suicide attempters and ideators during the acute suicidal episode

OBJECTIVE: To compare psychological and event-related contingencies that characterize and differentiate adolescent suicidal ideation and attempts. METHOD: Thirty-five ideators and 32 attempters (aged 12 to 17 years) consecutively referred to the suicide disorders clinic were evaluated with a semistructured interview about current and past emotional, cognitive, and behavioral states. RESULTS: Before the precipitant stressor (baseline), attempters reported significantly more hopelessness than ideators (odds ratio [OR] = 4.2, p < .05). During the suicidal episode, attempters, relative to ideators, spent more time ideating (OR = 4.3, p < .05), were more likely to isolate themselves (OR = 5.8, p < .01), and were less likely to tell anyone what they were thinking (OR = 4.5, p < .05). In contrast, ideators reported significantly more residual anger after the episode than did attempters (OR = 4.0, p < .05). All the episodes of ideation and attempts were preceded by a stress event. No differences were found between the groups on Beck Depression inventory scores. CONCLUSIONS: Preexisting hopelessness, a tendency toward isolation, not talking about ideation, and longer length of time ideating during suicidal episodes discriminated suicide attempters from suicide ideators. Knowledge of these factors may be helpful in preventive and treatment efforts with suicidal adolescents.     

Relation between depression and circulating immune products in patients with advanced colorectal cancer

We have previously suggested that colorectal liver metastases might produce 'toxins' that reduce both quality of life (QoL) and survival. In this study we assessed whether QoL in patients with such metastases was related to immune activation, as determined by increased serum levels of interleukin 6 (IL6), soluble tumour necrosis factor receptor 1 (sTNFr1), soluble interleukin 2 receptor alpha (sIL2r alpha) or the interferon-gamma marker neopterin. Serum IL6, sTNFr1, sIL2r alpha, neopterin, alkaline phosphatase and carcinoembryonic antigen levels, liver metastasis volume, and QoL (Hospital Anxiety and Depression [HAD] scale, Rotterdam Symptom Checklist [RSC], and Sickness Impact Profile [SIP]) were measured in 43 patients. There were significant positive correlations between serum sIL2r alpha and HAD depression score (r = 0.66, P = 0.0001), RSC physical symptom score (r = 0.46, P < 0.01), and SIP score (r = 0.47, P = 0.009). Multiple regression analysis suggested that serum sIL2r alpha level was a significant independent predictor of HAD depression score. Although survival was shorter (logrank test P < 0.05) where sIL2r alpha, sTNFr1 and IL6 levels were higher, the ability of sIL2r alpha to predict HAD depression score was independent of survival.     

The effect of injection speed on the pain of lidocaine infiltration

OBJECTIVE: To determine whether reducing the speed of injection is effective in reducing injection pain for buffered and unbuffered lidocaine solutions. METHODS: A prospective, single-blind, randomized, crossover, laboratory study was performed. Adult volunteers were recruited from ED staff at an urban teaching hospital to serve as subjects. Twenty-nine subjects each received 4 1-mL injections into the dorsum of the hands. Each subject received fast and slow injections of buffered and unbuffered lidocaine. Subjects rated the pain of each injection on a 100-mm visual analog scale (VAS). Mean pain scores for each intervention were compared using analysis of variance. RESULTS: The mean pain VAS score for fast injection of buffered lidocaine was 14.1 mm. For slow buffered injection, the mean pain score was 11.4 mm (p = 0.98). For unbuffered lidocaine, the means were 28.7 mm for fast injection and 22.2 mm for slow injection (p = 0.40). CONCLUSIONS: Reducing injection speed did not produce a statistically significant change in injection pain for either buffered or unbuffered solutions.