The diagnosis and management of Piriformis Syndrome: myths and facts.

Piriformis Syndrome (PS) is an uncommon, controversial neuromuscular disorder that is presumed to be a compression neuropathy of the sciatic nerve at the level of the piriformis muscle (PM). The diagnosis is hampered by a lack of agreed upon clinical criteria and a lack of definitive investigations such as imaging or electrodiagnostic testing. Treatment has focused on stretching, physical therapies, local injections, including botulinum toxin, and surgical management. This article explores the various sources of controversy surrounding piriformis syndrome including diagnosis, investigation and management. We conclude with a proposal for diagnostic criteria which include signs and symptoms, imaging, and response to therapeutic injections.

Panic and avoidance in agoraphobia. Application of path analysis to treatment studies.

We explored a causal sequence between panic and avoidance to provide recommendations for psychotherapy, pharmacotherapy, and their combination in treating agoraphobia. We produced a two-way [( imipramine hydrochloride vs placebo] by [office-based behavioral therapy vs in vivo exposure]) design by amalgamating two studies. We assessed agoraphobic patients for panic and avoidance at these time points: baseline (week 0), midcourse (week 13), and termination (week 26). The causal sequence model was tested by path analysis. Imipramine was superior to placebo in lowering panic and avoidance at both postbaseline time points. Exposure was superior to office-based treatment in lowering avoidance only at week 13. Exposure appeared to produce quicker improvement of avoidance than office-based therapy, but relapse occurred if this improvement was not supported by medication. Exposure did not benefit panic. We believe patients should be informed that imipramine is superior to exposure in inducing a panic-free state. Exposure without imipramine is of benefit only in reducing avoidance, but adding imipramine to exposure is necessary for panic control and substantially improves exposure and exposure maintenance.

A controlled trial of timed bright light and negative air ionization for treatment of winter depression.

BACKGROUND: Artificial bright light presents a promising nonpharmacological treatment for seasonal affective disorder. Past studies, however, have lacked adequate placebo controls or sufficient power to detect group differences. The importance of time of day of treatment--specifically, morning light superiority--has remained controversial. METHODS: This study used a morning x evening light crossover design balanced by parallel-group controls, in addition to a nonphotic control, negative air ionization. Subjects with seasonal affective disorder (N = 158) were randomly assigned to 6 groups for 2 consecutive treatment periods, each 10 to 14 days. Light treatment sequences were morning-evening, evening-morning, morning-morning, and evening-evening (10,000 lux, 30 min/d). Ion density was 2.7 x 10(6) (high) or 1.0 x 10(4) (low) ions per cubic centimeter (high-high and low-low sequences, 30 min/d in the morning). RESULTS: Analysis of depression scale percentage change scores showed low-density ion response to be inferior to all other groups, with no other group differences. Response to evening light was reduced when preceded by treatment with morning light, the sole sequence effect. Stringent remission criteria, however, showed significantly higher response to morning than evening light, regardless of treatment sequence. CONCLUSIONS: Bright light and high-density negative air ionization both appear to act as specific antidepressants in patients with seasonal affective disorder. Whether clinical improvement would be further enhanced by their use in combination, or as adjuvants to medication, awaits investigation.

Treatment of phobias. II. Behavior therapy and supportive psychotherapy: are there any specific ingredients?

Systematic hierarchical desensitization (behavior therapy [BT]) was compared with supportive psychotherapy (ST) during a 26-week treatment trial of patients with agoraphobia, mixed phobia, or simple phobia. We found essentially no difference in effectiveness, not because patients treated with BT had done badly, but because patients receiving ST had done well. A detailed methodologic review concludes that this finding is entirely compatible with the major critical reviews of the psychotherapy literature. Is the active ingredient in psychotherapy simply the generation of hopeful expectancies? This is necessary but not sufficient. For phobics, the psychotherapy session serves primarily as an instigator. The specific corrective activity occurs outside of the formal session in the form of maintained exposure in vivo. Supposed differences between therapies may be entirely due to the rapidly with which the instigational function becomes effective.

Treatment of phobias. I. Comparison of imipramine hydrochloride and placebo.

In a controlled-outcome study of phobias, 218 adult phobic patients (147 women and 71 men) received a course of 26 weekly treatment sessions that consisted of behavior therapy (BT) and imipramine hydrochloride, BT and placebo, or supportive psychotherapy and imipramine. The BT consisted of systematic desentization using fantasy and assertiveness training. Patients were classified as agoraphobic, mixed phobic, or simple phobic. Although the conditions of most patients in each group showed moderate to marked improvement, the effects of imipramine were significantly superior to those of placebo in patients with spontaneous panic attacks, ie, patients with agoraphobia or mixed phobia. In patients with simple phobia, who do not experience spontaneous panic, there was not a significant difference between imipramine and placebo. This study clearly distinguished those phobic patients who experienced spontaneous panic from those who did not in terms of pharmacologic benefits.

Body composition in affective disorder before, during, and after lithium carbonate therapy.

The body composition of three unipolar and 17 bipolar patients, studied during the depressive state, was compared with that of 48 controls. The ratio of extracellular to intracellular water content was significantly less in male patients than in male controls: the difference between female patients and female controls was not statistically significant. In patients of both sexes, residual sodium concentration was greater in patients than in controls. The intracellular content of potassium was the same in patients as in controls. In six patients, body composition was studied prior to lithium carbonate therapy, after 17 days of treatment, and 17 days after discontinuing administration of the drug. The significant changes were a decrease in body weight during therapy, and a decrease in body water content and an increase in residual sodium concentration after drug treatment was discontinued.

Predictors of response and nonresponse to light treatment for winter depression.

OBJECTIVE: The authors' goal was to determine whether the pattern and severity of depressive symptoms predict response to light treatment for seasonal affective disorder. METHOD: Subjects with winter depression (N = 103) were given bright light treatment. Seventy-one were classified as responders, 15 as nonresponders, and 17 as partial responders. Using depression rating scale data and correlational and multivariate analysis, the authors sought predictors of response in baseline symptom and scale scores. RESULTS: Responders were characterized by atypical symptoms, especially hypersomnia, afternoon or evening slump, reverse diurnal variation (evenings worse), and carbohydrate craving. By contrast, nonresponders were characterized mainly by melancholic symptoms, retardation, suicidality, depersonalization, typical diurnal variation (mornings worse), anxiety, early and late insomnia, appetite loss, and guilt. The ratio of atypical to classical symptoms of depression, rather than severity per se, best predicted treatment outcome for the group as a whole. Pretreatment expectations were positively correlated with improvement on the Hamilton Depression Rating Scale but not on a supplementary scale of atypical symptoms. CONCLUSIONS: Light-responsive seasonal affective disorder is distinguished by a dominant atypical symptom profile closely associated with depressed mood. Nonresponders from a clinically distinct group with melancholic features. The patient's symptom profile, therefore, should be considered when diagnosing seasonal affective disorder and selecting treatment.

Heterogeneity of clinical response during placebo treatment.

OBJECTIVE: The authors attempted to identify different patterns of improvement among patients receiving placebo during clinical trials. It was hypothesized that patients who improved abruptly would differ from patients whose improvement was gradual in that they would tend to improve earlier and would tend to have less persistent improvement. METHOD: The subjects were 144 patients who met the DSM-III criteria for depressive illness and were randomly assigned to placebo medication in four double-blind antidepressant drug trials. All studies lasted 6 weeks. Mood change was rated each week on a 7-point scale; a rating of 1 or 2 was considered an indication of improvement. Improvement was judged to be abrupt if the first score of 1 or 2 was immediately preceded by a score of 4 or worse, and it was classified as gradual if the first score of 1 or 2 was preceded by a score of 3 in at least 1 week. Improvement was considered persistent if a score of 1 or 2 was not followed by a score of 3 or worse in any subsequent week. RESULTS: Of the 144 patients, 72 showed clinical improvement during at least one weekly visit; 33 improved abruptly and 39 improved gradually. The abrupt improvements occurred significantly earlier in the trial and were less likely to persist than the gradual improvements regardless of when they occurred. CONCLUSIONS: These data suggest that among patients receiving placebo abrupt improvements are a form of placebo response and gradual responses may be the result of spontaneous remission. These preliminary observations require validation.

Different types of placebo response in patients receiving antidepressants.

OBJECTIVE: The authors studied the responses of drug-treated patients in an attempt to validate observations about abrupt and gradual improvements in patients receiving placebo. Since previous data suggested that in the first 2 weeks of antidepressant treatment specific drug effects are unlikely, the authors hypothesized that this improvement is a placebo effect. Therefore, in the first 2 weeks of antidepressant treatment abrupt and gradual improvements should have the characteristics of their placebo counterparts. METHOD: The subjects were 263 patients in controlled antidepressant trials lasting 6 weeks. RESULTS: The percentage of abrupt improvements that occurred in the first 2 weeks was higher than that for gradual improvements. Abrupt improvements during the first 2 weeks of drug treatment were also less persistent than gradual improvements with drug and no more persistent than improvements with placebo during the same period. However, in weeks 3, 4, and 5, abrupt and gradual improvements with drug were equally persistent and both were more persistent than abrupt improvements with placebo. CONCLUSIONS: These data support the authors' findings about placebo. Abrupt improvements during treatment with both drug and placebo are more likely during the first 2 weeks of treatment and are less likely to persist than gradual improvements. The fact that persistence of abrupt improvements with drug in weeks 1 and 2 appears different from that of gradual improvements but appears no different after week 3 suggests that the mechanism of action of abrupt improvement with drug changes after week 2.

Quinoline anti-malarial drugs inhibit spontaneous formation of beta-haematin (malaria pigment).

Polymerisation of haematin to beta-haematin (haemozoin or malaria pigment) in acidic acetate solutions was studied using infrared spectroscopy. The reaction was found to occur spontaneously between 6 and 65 degrees C, in 0.1-4.5 M acetate and pH 4.2-5.0. The anti-malarial drugs quinine, chloroquine and amodiaquin were found to block spontaneous beta-haematin formation, while the anti-malarially inactive 9-epiquinine and 8-hydroxyquinoline had no effect on the reaction, as did primaquine, a drug which is active only against exo-erythrocytic stages of infection. It is argued that the intra-erythrocytically active anti-malarial agents act by binding to haematin, blocking beta-haematin formation and leaving toxic haematin in the parasite food vacuoles.

Reanalysis of the National Institute of Mental Health Treatment of Depression Collaborative Research Program General Effectiveness Report.

The National Institute of Mental Health (NIMH) Treatment of Depression Collaborative Research Program General Effectiveness Report statistical analyses are criticized. Their analyses, which fostered the belief that criticized. Their analyses, which fostered the belief that the active treatments were indistinguishable, were compromised by an inappropriately stringent level of significance with regard to both heterogeneity of slope and pairwise group differences. Once slope heterogeneity is detected, the Johnson-Neyman technique is more appropriate than arbitrary sample subdivision. All of these tactics lowered power substantially. Our reanalysis indicates a reasonable ordering for the treatments with medication superior to the psychotherapies and the psychotherapies somewhat superior to placebo. These effects are particularly marked among the more symptomatic and impaired patients. The lack of dosage by severity analyses renders the severity findings ambiguous. Scientific and public health implications are discussed.

Using severity rather than randomization for assignment in clinical trials: Monte Carlo tests and practical illustrations of the Robbins-Zhang method.

In randomized clinical trials, patients are not differentially assigned to treatments by severity because available methods of data analysis are sensitive to regression to the mean and yield biased estimates of treatment effect. However, a method proposed by Robbins and Zhang provides consistent estimates of treatment effect in clinical trials, even when the more severely ill are assigned to the active treatment and the less severely ill are assigned to a placebo. This method was assessed by Monte Carlo trials. All combinations of two models of drug effect, five true score distributions, four magnitudes of error variance, and four sample sizes were assessed. The method works sufficiently well that its use should be considered. Further, the method gives correct results even when the regression discontinuity method fails. The method was also compared with a standard analysis of variance of difference scores using real psychiatric data from two ordinary randomized trials; similar results were obtained by both methods.

Toxic and antifeeding actions of melittin in the corn earworm, Heliothis zea (Boddie): comparisons to bee venom and the insecticides chlorpyriphos and cyromazine.

The acute and sublethal effects of melittin were compared to whole bee venom, chlorpyriphos and cyromazine injected into the corn earworm, Heliothis zea (Boddie). Melittin had twice the toxicity of crude venom, but only 3% that of chlorpyriphos. Melittin significantly reduced growth rate, diet consumption and food utilization efficiencies of fourth instar larvae. Bee venom and insecticides reduced these parameters to a lesser extent.

Thermodynamic factors controlling the interaction of quinoline antimalarial drugs with ferriprotoporphyrin IX.

The interaction of a variety of quinoline antimalarial drugs as well as other quinoline derivatives with strictly monomeric ferriprotoporphyrin IX [Fe(III)PPIX] has been investigated in 40% aqueous DMSO solution. At an apparent pH of 7.5 and 25 degrees C, log K values for bonding are 5.52 +/- 0.03 (chloroquine), 5.39 +/- 0.04 (amodiaquine), 4.10 +/- 0.02 (quinine), 4.04 +/- 0.03 (9-epiquinine), and 3.90 +/- 0.08 (mefloquine). Primaquine, 8-hydroxyquinoline, 5-aminoquinoline, 6-aminoquinoline, 8-aminoquinoline, and quinoline exhibit no evidence of interaction with Fe(III)PPIX. The enthalpy and entropy changes for the interaction of quinolines with Fe(III)PPIX, as determined from the temperature dependence of the log K values, exhibit a compensation phenomenon that is suggestive of hydrophobic interaction. This is supported by the finding that the interactions of chloroquine and quinine with Fe(III)PPIX are weakened by increasing concentrations of acetonitrile. Interactions of chloroquine, quinine, and 9-epiquinine with Fe(III)PPIX are shown to remain strong at pH 5.6, the approximate pH of the food vacuole of the malaria parasite which is believed to be the locus of drug activity. Implications for the design of antimalarial drugs are briefly discussed.

Normalization of venous pH, pCO2, and bicarbonate levels after blockade of panic attacks.

Recent evidence suggests that hyperventilation may be associated with spontaneous panic attacks in patients with panic disorder. This is reflected in abnormal patterns of blood gas and blood pH levels in these patients. In this study, absolute levels and variances of pH, pCO2, and bicarbonate were compared between controlled patients before and after successful pharmacological treatment. The results indicate that successful treatment of panic disorder results in a normalization of pH, pCO2, and bicarbonate levels.

Are patients satisfied with results from residents performing aesthetic surgery?

An 8-year survey of patient satisfaction in an academic aesthetic surgery clinic at the University of Toronto was carried out by means of a mailed questionnaire. A total of 265 questionnaires were mailed; 131 completed questionnaires (49.4 percent) were returned. Of these, 93.1 percent would recommend this clinic (88.1 percent in the first year of operation and 95.4 percent in the subsequent 7 years), and 92.9 percent would undergo the same procedure again, if required (88.3 percent in the first year and 95.0 percent in the next 7 years). The highest patient satisfaction (10 of 10) was seen in augmentation mammoplasty (average, 9.1); blepharoplasty (average, 9.0); rhytidectomy (average, 7.8), and rhinoplasty (average, 6.9). The results obtained compared favorably with recently published data of more experienced surgeons.

Upper limb Escherichia coli cellulitis in the immunocompromised.

The neutropenic state characteristic of acute lymphoblastic leukaemia (ALL) predisposes to infections involving Gram-negative bacilli. An Escherichia coli cellulitis originating in the first web space of the hand is described in a patient undergoing reinduction chemotherapy for ALL. Proximal extension of the infection progressed at a very rapid rate and required a forequarter amputation as a life saving measure. Due to the blunted inflammatory response in neutropenic patients, the need for close monitoring and quick intervention is stressed.

Epidemiology of Dupuytren's disease.

Studying the epidemiology of Dupuytren's disease allows the identification of populations at risk and may point to inferences regarding etiology. Data suggest the highest prevalence of the disease occurs in people of northern European stock. However, the disease does occur in nearly all populations examined. Dupuytren's disease occurs more frequently in men than women and becomes symptomatic approximately 10 years earlier in the lives of men than in women. Dupuytren's disease has been associated with a number of other diseases including seizure disorders, alcoholism, diabetes mellitus, and cigarette smoking. There is conflicting evidence as to whether manual labor or HIV seropositivity increases the prevalence of the disorder.