Guidelines for Trials of Behavioral Treatments for Recurrent Headache, First Edition: American Headache Society Behavioral Clinical Trials Workgroup

Guidelines for design of clinical trials evaluating behavioral headache treatments were developed to facilitate production of quality research evaluating behavioral therapies for management of primary headache disorders. These guidelines were produced by a Workgroup of headache researchers under auspices of the American Headache Society. The guidelines are complementary to and modeled after guidelines for pharmacological trials published by the International Headache Society, but they address methodologic considerations unique to behavioral and other nonpharmacological treatments. Explicit guidelines for evaluating behavioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharmacologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials comparing and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. These guidelines address patient selection, trial design for behavioral treatments and for comparisons across multiple treatment modalities (eg, behavioral vs pharmacologic), evaluation of results, and research ethics. Although developed specifically for behavioral therapies, the guidelines may apply to the design of clinical trials evaluating many forms of nonpharmacologic therapies for headache.     

Behavioral, biochemical and neurotoxicological actions of the alpha-ethyl homologue of p-chloroamphetamine

The present set of experiments was designed to examine the effects of extension of the alpha-methyl of p-chloroamphetamine (PCA) to an alpha-ethyl. Therefore, the alpha-ethyl homologue of PCA, 1-(4-chlorophenyl)-2-aminobutane (CAB), was compared to PCA in a number of pharmacological assays. CAB was 2-fold less potent than PCA at inhibiting synaptosomal uptake of [3H]5-hydroxytryptamine ([3H]5-HT), and 5-fold less potent at inhibiting uptake of [3H]dopamine ([3H]DA). In drug discrimination assays, CAB was approximately 3-fold less potent than PCA in animals trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or its alpha-ethyl homologue, S-(+)-N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (S-(+)-MBDB), from saline. Monitoring with in vivo microdialysis, 10 mg/kg of PCA caused a large increase in extracellular DA and a significant decrease in 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum. In contrast, 11 mg/kg CAB caused no increase and 22 mg/kg CAB caused only a slight increase in extracellular DA. Both doses of CAB caused a decrease in extracellular DOPAC. The potential 5-HT neurotoxicity of CAB was examined by measuring monoamine and metabolite levels and [3H]paroxetine binding at one week following acute doses. A 10 mg/kg dose of PCA caused an 80% decrease in cortical and hippocampal serotonergic markers, while an equimolar dose of CAB decreased only hippocampal 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels. However, 22 mg/kg of CAB produced a 20-40% decrease in all serotonergic markers. Thus, extension of the alpha-alkyl significantly decreases the dopaminergic effects of PCA. The similar decrease in relative 5-HT neurotoxicity and the decreased ability to alter dopaminergic systems in vivo and in vitro supports the involvement of DA in the neurotoxicity of PCA.     

The effects of a 0.12% chlorhexidine-digluconate-containing mouthrinse versus a placebo on plaque and gingival inflammation over a 3-month period

Abstract Several previous studies have evaluated the effects of 0.12% chlorhexidine digluconate (ChD) mouthrinses on plaque and gingival inflammation. However, previously, none have been based in general dental practices. The aim of this study was to evaluate the potential to conduct controlled periodontal clinical trials in co-operation with general dental practitioners (gdps). The project took place in 5 general dental practices in the South of England. 121 healthy subjects (24 at 4 sites and 25 at the 5th). aged 18-65 years, mean 35 ± 12) years participated in a double-blind, randomised study during which they received full mouth assessments for plaque and gingival bleeding at baseline, 6 and 12 weeks. 60 subjects were randomly asigned to use the 0.12% ChD mouth wash and 6i the placebo. The assessments were carried out by 5 gpds, who had previously achieved inter-examiner κ scores of 0.78–0.85 (mean 0.81) for the plaque index (PlI), and of 0.73–0.94 (mean 0.87) for a modified gingival index (mGI), and who maintained κ scores of 0.51–0.90 for PII and of 0.73–1.00 for mGI during the 12 months required to complete the study. 98 subjects (48 ChD and 50 placebo) completed the study. Even though the baseline levels of plaque and gingivitis were low, by week 12, mean whole mouth piaque score of the ChD mouthwash users had fallen from 1.33 at baseline to 0.96 and was significantly lower (p < 0.001) than for the placebo users, 1.31 at baseline to 1.13. Whole-mouth gingival bleeding score fell from 0.56 to 0.42 in the ChD mouthwash group but was unchanged (0.54–0.55) in the placebo group. A subsidiary data analysis which considered the effects at sites indicated that within these overall differences, the ChD users experienced almost 2× the reduction from plaque score 2 at baseline at proximal molar sites over a 12-week period (50.6% ChD versus 27.6% placebo). It was concluded that 0.12% ChD mouthwash reduced plaque accumulation fay 28% and gingival inflammation by 25% over a 12–week period, that it is feasible for a group of gdps to maintain high levels of inter–examiner consistency in the use of PlI and mGI, that it is also feasible to carry out such a multicentre study in general dental practice, and that the use of mean mouth scores per subject to analyse the effects of mouthrinses may well mask variations in response throughout the mouth.     

A comparison of pharmacological (amitriptyline HCL) and nonpharmacological (cognitive-behavioral) therapies for chronic tension headaches

Forty-one recurrent tension headache sufferers were randomly assigned to either cognitive-behavioral therapy (administered in a primarily home-based treatment protocol) or to amitriptyline therapy (with dosage individualized at 25, 50, or 75 mg/day). Cognitive-behavioral therapy and amitriptyline each yielded clinically significant improvements in headache activity, both when improvement was assessed with patient daily recordings (56% and 27% reduction in headache index, respectively), and when improvement was assessed with neurologist ratings of clinical improvement (94% and 69% of patients rated at least moderately improved, respectively). In instances where differences in treatment effectiveness were observed (headache index, somatic complaints, perceptions of control of headache activity), cognitive-behavioral therapy yielded somewhat more positive outcomes than did amitriptyline. Neither treatment, however, eliminated headache problems.     

Mandibular fracture not shown by axial computed tomography: Benefit of computed reformation

A 36-year-old man was brought to the emergency department after being assaulted. A mandible series showed a nondisplaced fracture through the angle of the mandible extending through the left third molar tooth. Axial slices from a nonhelical computed tomographic (CT) examination of the head as well as a helical CT examination of the mandible failed to demonstrate the fracture. The fracture was well shown, however, on sagittal CT reformations. Although CT is generally regarded as more sensitive than plain radiography for the detection of fractures, fractures may be overlooked by CT if examination in only one plane is performed.     

Value of grading squamous cell carcinoma of the head and neck.

We report a series of 3,294 patients with squamous cell carcinoma of the head and neck seen by one of us between 1963 and 1990. Two thousand and seven patients had a histologically proven and graded, but previously untreated, squamous cell carcinoma of the mucosal surfaces of the head and neck. These tumors had been graded previously by many different pathologists in many different hospitals, both in the United Kingdom and the United States, as well as continental Europe, over this period. Of the host factors both sex and age were associated with differentiation: 34% of patients less than age 50 had a well-differentiated tumor compared with 44% greater than age 50; 32% of women had a poorly differentiated tumor compared with 26% of men. General condition had no correlation with degree of differentiation. Site was closely associated with grading: well-differentiated tumors were more common in the mouth and larynx and poorly differentiated tumors in the pharynx. Furthermore, of poorly differentiated tumors, 19% arose from areas normally lined by keratinized squamous epithelium, 22% from a nonkeratinized area, 36% from respiratory epithelium, and 45% from areas normally covered by lymphoid epithelium. T stage had no significant correlation with differentiation. However, 46% of patients with poorly differentiated tumors had a nodal metastasis at presentation compared with only 28% of well-differentiated tumors. Distant metastases at presentation were found in 3.4% of poorly differentiated tumors compared with 1.8% of well-differentiated tumors. The survival fell significantly from 33% for well-differentiated tumors to 27% for poorly differentiated tumors. The recurrence rate at the primary site rose from 25% for well-differentiated tumors to 27% for poorly differentiated tumors, and recurrence in the lymph nodes rose from 26% to 30%. Both differences were just significant.     

Human cellular immune response to Giardia lamblia

Summary Human peripheral blood mononuclear cells (PBMC) from two individuals experimentally and one naturally infected withGiardia lamblia responded strongly (in anin vitro lymphocyte proliferation assay) to both heterologous and homologous (parasite origin)G. lamblia antigen stimuli. Proliferative responses to specific antigens as determined by T-cell blotting were due toGiardia T-cell epitopes mostly present in antigens lower than M_r 85,000 and 31,000 in isolates PM and GS/M-H7, respectively. Additionally, Il-2 production of PBMC respective to T lymphocyte subsets under antigen stimulation were determined in one selected patient. Proliferative and lymphokine responses could be associated with CD4⁺ PBMC depleted of CD8⁺ T cells and not with PBMC depleted of CD4⁺ T cells. These preliminary results suggest the initiation of larger studies addressing questions of cell-mediated immune response and the role of lymphokines in human giardiasis.

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Zelluläre Immunreaktion gegen Giardia lamblia beim Menschen

Zusammenfassung Periphere Blutmonozyten von zwei Personen mit einer experimentell und einer mit einer natürlich erworbenenGiardia lamblia-Infektion zeigten eine ausgeprägte lymphoproliferative Antwort nachIn-vitro-Stimulation mit Parasitenantigen, das sowohl aus homologen als auch heterologen Parasitenisolaten gewonnen worden war. Eine T-Zell-Blot- Analyse der lymphoproliferativen Immunantwort bezüglich der nach Molekulargewicht aufgetrenntenGiardia-Antigenkomponenten zeigte, daß das Spektrum derGiardia-Antigene mit T-Zell-Epitopen im M_r-Bereich von < 85'000 für das PM-1-Isolat und < 31'000 für das GS/M-H7-Isolat lagen. Bei einem der Patienten wurden Lymphozyten nach antigen-spezifischerIn-vitro-Proliferation auf ihre Lymphozytensubpopulationen und deren Fähigkeit zur Il-2-Produktion untersucht. Eine lymphoproliferative Antwort, verkoppelt mit einer Il-2-Produktion, war nur bei CD4⁺ Lymphozyten (nach entsprechender Eliminierung von CD8⁺ Lymphozyten) und nicht bei CD8⁺ Lymphozyten (nach entsprechender Eliminierung von CD4⁺ Lymphozyten) nachweisbar.