Characterizing problematic hypoglycaemia: iterative design and preliminary psychometric validation of the Hypoglycaemia Awareness Questionnaire (HypoA-Q).

AIMS: To design and conduct preliminary validation of a measure of hypoglycaemia awareness and problematic hypoglycaemia, the Hypoglycaemia Awareness Questionnaire. METHODS: Exploratory and cognitive debriefing interviews were conducted with 17 adults (nine of whom were women) with Type 1 diabetes (mean ± sd age 48 ± 10 years). Questionnaire items were modified in consultation with diabetologists/psychologists. Psychometric validation was undertaken using data from 120 adults (53 women) with Type 1 diabetes (mean ± sd age 44 ± 16 years; 50% with clinically diagnosed impaired awareness of hypoglycaemia), who completed the following questionnaires: the Hypoglycaemia Awareness Questionnaire, the Gold score, the Clarke questionnaire and the Problem Areas in Diabetes questionnaire. RESULTS: Iterative design resulted in 33 items eliciting responses about awareness of hypoglycaemia when awake/asleep and hypoglycaemia frequency, severity and impact (healthcare utilization). Psychometric analysis identified three subscales reflecting 'impaired awareness', 'symptom level' and 'symptom frequency'. Convergent validity was indicated by strong correlations between the 'impaired awareness' subscale and existing measures of awareness: (Gold: rs =0.75, P < 0.01; Clarke: rs =0.76, P < 0.01). Divergent validity was indicated by weaker correlations with diabetes-related distress (Problem Areas in Diabetes: rs =0.25, P < 0.01) and HbA1c (rs =-0.05, non-significant). The 'impaired awareness' subscale and other items discriminated between those with impaired and intact awareness (Gold score). The 'impaired awareness' subscale and other items contributed significantly to models explaining the occurrence of severe hypoglycaemia and hypoglycaemia when asleep. CONCLUSIONS: This preliminary validation shows the Hypoglycaemia Awareness Questionnaire has robust face and content validity; satisfactory structure; internal reliability; convergent, divergent and known groups validity. The impaired awareness subscale and other items contribute significantly to models explaining recall of severe and nocturnal hypoglycaemia. Prospective validation, including determination of a threshold to identify impaired awareness, is now warranted.

Severe hypoglycaemia in type 1 diabetes mellitus: underlying drivers and potential strategies for successful prevention.

Hypoglycaemia remains an over-riding factor limiting optimal glycaemic control in type 1 diabetes. Severe hypoglycaemia is prevalent in almost half of those with long-duration diabetes and is one of the most feared diabetes-related complications. In this review, we present an overview of the increasing body of literature seeking to elucidate the underlying pathophysiology of severe hypoglycaemia and the limited evidence behind the strategies employed to prevent episodes. Drivers of severe hypoglycaemia including impaired counter-regulation, hypoglycaemia-associated autonomic failure, psychosocial and behavioural factors and neuroimaging correlates are discussed. Treatment strategies encompassing structured education, insulin analogue regimens, continuous subcutaneous insulin infusion pumps, continuous glucose sensing and beta-cell replacement therapies have been employed, yet there is little randomized controlled trial evidence demonstrating effectiveness of new technologies in reducing severe hypoglycaemia. Optimally designed interventional trials evaluating these existing technologies and using modern methods of teaching patients flexible insulin use within structured education programmes with the specific goal of preventing severe hypoglycaemia are required. Individuals at high risk need to be monitored with meticulous collection of data on awareness, as well as frequency and severity of all hypoglycaemic episodes.

A 45Ca autoradiographic and stereological study of freeze-dried smooth muscle of the guinea pig vas deferens.

In an effort to more clearly elucidate the role of cellular structures as calcium sinks and sources in smooth muscle cells, the intracellular distribution of radioactive calcium was evaluated by a new method based on freeze-drying. The guinea pig vas deferens was exposed to a physiological salt solution that contained 45Ca. The muscle was then freeze-dried and prepared for electron microscope autoradiography. The grain density over the plasma membrane, mitochondria, and sarcoplasmic reticulum (SR) was significantly greater than that of the matrix. These results suggest that the plasma membrane, mitochondria and SR have the capacity to accumulate calcium. Which of these structures serve as a source of calcium for contraction remains to be determined. A stereological comparison between freeze-dried and conventionally prepared smooth muscles revealed several differences. The cross-sectional area of freeze-dried cells was about twice that of conventionally prepared cells. Moreover, mitochondria and sub-surface vesicles occupied a significantly smaller percentage of the cell in the freeze-dried tissue than they did in the conventionally prepared tissue.

An evidence-based approach to the child who drools saliva.

BACKGROUND: Drooling is a common dysfunction in children with cerebral palsy and may also affect neurologically unimpaired children. It causes significant social handicap to both children and their families. METHODS: The data in this article are supported by a Medline search (November 2008) utilising the keywords drooling, sialorrhea, botulinum toxin, salivary duct ligation and also by the use of the personal bibliographies of the senior authors. RESULTS: The majority of the published literature for drooling is of level III/IV evidence. CONCLUSION: Multiple therapeutic interventions are available for paediatric drooling. These are most appropriately introduced in a stepwise progression from behaviour therapy, to pharmacotherapy to surgical procedures.

Nasal disease and quality of life in athletes.

OBJECTIVES: Nasal disease imposes a significant disease burden upon the individual in the general population, but is relatively under studied in athletes. This study sought to define the frequency of nasal symptoms in the active population, and to quantify the impact of these symptoms on quality of life and on the frequency of upper respiratory tract infections. RESULTS: A total of 296 participants completed the study (246 athletes and 50 sedentary controls). Nasal symptoms were significantly more frequent in the active group than in the sedentary controls (70 per cent vs 52 per cent). Upper respiratory tract infections were significantly more common in athletes with regular nasal symptoms than in athletes without nasal symptoms. Quality-of-life scores, as measured by the 22-item Sino-Nasal Outcome Test, were significantly worse in athletes with regular nasal symptoms. CONCLUSION: This study suggests that regular exercise is associated with a significant increase in the prevalence of troubling nasal symptoms, and nasal symptoms in athletes are associated with increased susceptibility to upper respiratory tract infections. Quality of life was negatively affected, confirming the importance of nasal health to athlete welfare.

Characterization of proinsulin-insulin intermediates in human plasma.

This work addressed the problem of heterogeneity of immunoreactive insulin (IRI) in human plasma. Subjects with normal glucose tolerance were given 75g of an oral glucose solution, followed in 30 min by an intravenous infusion of 30g of arginine over 30 min. At the end of the infusion blood was withdrawn for analysis. IRI was extracted from plasma of individual subject by immunosorbent columns and was fractionated by gel filtration, disc gel electrophoresis and isoelectric focusing. Human IRI components were identified by molecular size, immunoreactivity with a human proinsulin antibody, sensitivity to trypsin, and by comparison of electrophoretic mobility and isoelectric point with porcine pancreatic products, after suitable correction for electric charge and molecular weight differences. The pattern of IRI heterogeneity was the same among six healthy subjects. Heterogeneity of proinsulin-size IRI in circulation was more marked than that of insulin-size material. Proinsulin and desdipeptide proinsulin were present in approximately equal amounts accompanied by minor amounts of split proinsulin and monodesamido-desdipeptide proinsulin. Insulin-size IRI contained over 80% insulin. Minor amounts of monodesamidoinsulin and diarginylinsulin were observed in some cases. The types of IRI components observed in plasma are evidence in support of a physiologic role of trypsin-and carboxypeptidase B-like enzymes in the conversion of proinsulin to insulin. Moreover, this study provides a base line for investigation of abnormalities in proinsulin-to-insulin conversion that may be associated with certain pathologic states.

Use of complementary and alternative medicine in pediatric otolaryngology patients attending a tertiary hospital in the UK.

OBJECTIVE: Little data is available on complementary and alternative medicine (CAM) use in children attending otolaryngology services. We investigated the prevalence and pattern of CAM use among children attending the pediatric otolaryngology department in a tertiary pediatric teaching hospital in Scotland. DESIGN: A cross-sectional survey conducted by administering an anonymous questionnaire to the parents accompanying patients attending the pediatric otolaryngology department. Elective admissions and clinic attendees were included over a 3-month period in 2005/2006. SETTING: Academic tertiary care referral centre in North-East Scotland. PATIENTS: Five hundred and fifty-four consecutive patients aged less than 16 years were eligible. The response rate was 59% (n=327). MAIN OUTCOME MEASURES: Prevalence of CAM use in children. Secondary measures include types of CAM used, indications for use and communication with family physicians. RESULTS: Based on 327 responses, 93 patients (29%) had ever used CAM, 20% within the last year. Commonly used CAM preparations were cod-liver oil, echinacea, aloe vera, cranberry, primrose oil and herbal vitamin supplements. The popular non-herbal CAM included homeopathy, massage, aromatherapy, chiropractic, yoga and reiki. Nineteen percent used CAM for their admission illness. Sixty-one percent of parents thought that CAM was effective and 65% would recommend it to others. Fifty-one percent of parents stated that the family physician was unaware of CAM use by the child. CONCLUSIONS: Despite concerns regarding the efficacy, safety and cost effectiveness of complementary and alternative medicine, its use among the pediatric otolaryngology population is more common than many providers may realize. This has implications for all healthcare workers involved in their care.

DNA cross-linking and single-strand breaks induced by teratogenic concentrations of 4-hydroperoxycyclophosphamide and phosphoramide mustard in postimplantation rat embryos.

Postimplantation rat embryos (Day 10) were exposed in vitro to teratogenic concentrations of 4-hydroperoxycyclophosphamide, an activated form of cyclophosphamide, and phosphoramide mustard, the major teratogenic metabolite of cyclophosphamide. Following a 5-h exposure to these agents, drug-induced DNA damage was assessed by alkaline elution. Both drugs induced detectable DNA cross-linking at teratogenic concentrations. Alkaline elution combined with proteinase K digestion indicated that approximately half of the DNA cross-linking was DNA-DNA cross-linking and the other half was DNA-protein cross-linking. In addition to DNA cross-linking, phosphoramide mustard produced DNA strand breaks and/or alkaline labile sites. However, 4-hydroperoxycyclophosphamide did not produce detectable DNA strand breaks or alkaline labile sites. Our data also indicate that the induction of abnormal morphogenesis by 4-hydroperoxycyclophosphamide and phosphoramide mustard is correlated with drug-induced DNA cross-linking.

Teratogen-induced cell death in postimplantation mouse embryos: differential tissue sensitivity and hallmarks of apoptosis.

Teratogen-induced cell death is a common event in the pathogenesis associated with tissues destined to be malformed. Although the importance of this cell death is recognized, little information is available concerning the biochemistry of teratogen-induced cell death. We show that three teratogens, hyperthermia, cyclophosphamide and sodium arsenite induce an increase in cell death in day 9.0 mouse embryos with concurrent induction of DNA fragmentation, activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP). Teratogen-induced cell death is also selective, i. e., some cells within a tissue die while others survive. In addition, cells within some tissues die when exposed to teratogens while cells in other tissues are relatively resistant to teratogen-induced cell death. An example of the latter selectivity is seen in the cells of the developing heart, which are resistant to the cytotoxic potential of many teratogens. We show that the absence of cell death in the heart is accompanied by the complete lack of DNA fragmentation, activtion of caspase-3 and the cleavage of PARP.

Characterization of prostaglandin E2 binding to isolated human adipocytes.

Prostaglandin (PG) E2 binding to fat cells and its consequent antilipolytic effect have been studied in experiments using laboratory animals, but no binding studies have yet been reported using adipocytes from humans. Consequently, we have characterized PGE2 binding to human isolated fat cells to compare the apparent binding constant to the IC50 for the antilipolytic effect of PGE2. Our data indicate that human fat cells contain binding sites that specifically recognize prostaglandins of the E series and demonstrate stereospecific recognition of the more potent of two 15-methyl-PGE2 analogues. There was no evidence for rapid metabolism of PGE2 by isolated adipocytes such as occurs in lung and liver tissue. A double-reciprocal plot of binding data obtained at saturation using [3H]PGE2 and increasing concentrations of PGE2 indicated a single class of binding sites with an apparent binding constant (0.54 nM) that agreed well with the IC50 (0.26 nM) for the antilipolytic effect of PGE2 we observed in human fat cells. The findings from these binding and lipolysis studies are in general agreement with published observations using adipocytes from rodents and provide evidence that the conclusions reached from previous studies of laboratory animals are relevant to adipocyte physiology in humans.

Receptor-mediated adenylate cyclase-coupled mechanism for PGE2 inhibition of insulin secretion in HIT cells.

Prostaglandin E2 (PGE2) inhibits glucose-induced insulin secretion, and inhibitors of PGE2 synthesis augment this event. However, there has been confusion regarding prostaglandin regulation of insulin secretion, partly because no mechanism has been demonstrated for the inhibitory action of PGE2 on beta-cell function. These studies were performed with a clonal cell line of glucose-responsive beta-cells (HIT cells) to determine whether PGE2 effects on insulin secretion are receptor mediated and, if so, whether the postreceptor effects are mediated by inhibitory regulatory components (Ni) of adenylate cyclase. Saturable [3H]PGE2 binding to HIT cells was demonstrated. This binding was dissociable and specific for prostaglandins of the E series. Scatchard analyses of binding data indicated a single class of sites with a Kd of approximately 1 X 10(-9) M. Guinea pig islets were also demonstrated to have a single class of binding sites with a similar Kd but only 22% as many binding sites (0.060 vs. 0.013 pmol/mg protein, HIT cells vs. guinea pig islet). HIT cells were demonstrated to synthesize PGE2, and this synthesis was inhibitable by acetylsalicylic acid. Accumulation of cAMP by HIT cells was inhibited in a concentration-dependent manner by PGE2 with an IC50 of approximately 1 X 10(-9) M. Insulin secretion by HIT cells during static incubations with 11.1 mM glucose was also inhibited by PGE2 in a concentration-dependent manner with an IC50 of 1 X 10(-9) M. PGE2 was more potent than epinephrine but less potent than somatostatin in this regard. Maximum inhibition of glucose-induced insulin secretion was 26, 37, and 29% of control values for somatostatin, PGE2, and epinephrine, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Down-regulation of prostaglandin E receptors and homologous desensitization of isolated adipocytes.

Adipocytes are known to contain prostaglandin E (PGE) binding sites and PGE is known to be antilipolytic. These studies were performed to ascertain whether PGE binding sites in isolated adipocytes can be down-regulated and whether down-regulation (DR) decreases the sensitivity of the fat cell to the antilipolytic effects of PGE2, adenosine, and insulin. Treatment in vivo of Sprague-Dawley rats with 16,16-dimethyl-PGE2, a PGE analog, induced DR of PGE-specific binding site density in both intact fat cells (175 vs. 307 fmol/mg protein) and triglyceride-free broken fat cell preparations (148 vs. 360 fmol/mg protein). There were no changes in binding affinities. DR was associated with diminished antilipolytic potency of PGE on basal glycerol production by intact fat cells in the presence of adenosine deaminase (IC50/control = 0.31 +/- 0.03 X 10(-9) M vs. DR = 1.6 +/- 0.03 X 10(-9) M; P less than 0.01). In contrast, there was no desensitization of the adipocytes to the antilipolytic effects of phenylisopropyladenosine (IC50/control = 4.65 +/- 0.96 X 10(-10) M vs. DR = 4.90 +/- 0.82 X 10(-10) M; P = NS) or insulin (IC50/control = 4.40 +/- 0.57 X 10(-11) M vs. DR = 2.70 +/- 0.24 X 10(-11); P = NS). PGE desensitization was also observed during studies of isoproterenol-stimulated lipolysis. These data uniquely demonstrate that the adipocyte PGE receptor can be down-regulated and that this decrease in PGE receptor density is associated with homologous desensitization of the fat cell to the antilipolytic effect of PGE and not adenosine or insulin. These findings suggest that a PGE-specific receptor may be involved in regulation of lipolysis by PGE.

Hepatocellular carcinoma: current surgical management.

At present the only potentially curative treatment for hepatocellular carcinoma (HCC) is either partial hepatectomy or total hepatectomy with orthotopic liver transplantation (OLT). Underlying liver reserve and regenerative capacity are the most important determinants of the risk of postoperative hepatic failure after partial hepatectomy; thus, careful preoperative assessment of liver function is mandatory. In specialized centers perioperative mortality is less than 5%, although cirrhotic patients are at increased risk. Various neoadjuvant and adjuvant therapies are under investigation, but as yet there are no data that demonstrate benefit from adjuvant systemic chemotherapy. The use of OLT is limited by the difficulty of obtaining donor livers. Patients selected for transplantation and partial hepatectomy represent two distinct subgroups, but their survival after treatment is comparable. Despite the progress in the management of HCC by surgical resection, the fact remains that the majority of these patients will experience local recurrences. This has led to the development of a variety of novel new treatments that require further evaluation.

Ultrastructural characteristics of freeze-dried smooth muscle.

The rapid freezing and vacuum dehydration of tissue has been employed to study the intracellular distribution of diffusible substances at the electron microscopic level. Hower, the ultrastructural detail of freeze-dried tissue is difficult to retain. Consequently, the ultrastructural preservation of freeze-dried smooth muscle has not been sufficient to permit satisfactorily definition of intracellular organelles. Therefore, determinations of the intracellular distribution of soluble ions have not been achieved in freeze-dried smooth muscle. In this study a freeze drying method is presented which provides more satisfactory definition of intracellular organelles than has been available in the past. Using this merens have been preserved. When these muscles are compared to convention preparer of surface vesicles that are observed, and the mitochondria are extremely electron opaque in the freeze-dried tissue. The smooth muscles which have been examined do not have the inherent contrast of other types of tissue nor do they contain the different types of mitochondria that have been observed in nonmuscle tissue.

Venlafaxine in the treatment of dysthymia: an open-label study.

BACKGROUND: Numerous studies have demonstrated the effectiveness of antidepressant medications in the treatment of dysthymia, or chronic mild depression. Venlafaxine blocks reuptake of both serotonin and norepinephrine and may produce a more complete antidepressant response than do single-mechanism selective serotonin reuptake inhibitors. The purpose of this open-label study was to provide preliminary data on the tolerability and effectiveness of venlafaxine for patients with dysthymia. METHOD: Twenty-two dysthymic subjects (DSM-III-R criteria) were enrolled in this 10-week, open-label trial, and 5 dropped out prior to their second visit. Seventeen subjects (77.3%) received more than 1 week of medication. RESULTS: Of these 17 subjects, 13 (76.5%) were treatment responders. Results of paired sample t tests were highly significant, indicating that, on average, there was significant improvement on all measures of symptomatology and functioning, with mean +/- SD scores on the Hamilton Rating Scale for Depression decreasing from 20.95 +/- 6.50 at baseline to 6.06 +/- 5.49 at week 10. The mean +/- SD final dose was 178.68 +/- 70.80 mg/day. Side effects were reported by 17 (85%) of the 20 subjects for whom tolerability was assessed (the most common were fatigue, dry mouth, and nausea); 5 (22.7%) of 22 patients discontinued treatment because of side effects, primarily nausea (N = 3). CONCLUSION: These findings suggest the benefit of venlafaxine in the treatment of chronic depression and the need for more rigorous studies.

Effect of infused angiotensin II on the bronchoconstrictor activity of inhaled endothelin-1 in asthma.

STUDY OBJECTIVES: Endothelin (ET)-1 is a potent bronchoconstrictor, and asthmatics demonstrate bronchial hyperresponsiveness to ET-1 given by inhalation. Angiotensin II (Ang II) is increased in plasma in acute severe asthma, causes bronchoconstriction in asthmatics, and potentiates contractions induced by ET-1 in bovine bronchial smooth muscle in vitro, and contractions induced by methacholine both in vitro and in vivo. We wished to examine any potentiation of the bronchoconstrictor activity of inhaled ET-1 by infused Ang II at subbronchoconstrictor doses. DESIGN: Double-blind randomized placebo-controlled study. SETTING: Asthma research unit in university hospital. PATIENTS: Eight asthmatic subjects with baseline FEV1 88% predicted, bronchial hyperreactivity (geometric mean, concentration of methacholine producing 20% fall, methacholine PC20 2.5 mg/mL), and mean age 37.1 years. INTERVENTIONS: We examined the effect of subbronchoconstrictor doses of infused Ang II (1 ng/kg/min and 2 ng/kg/min) or placebo on bronchoconstrictor responses to inhaled ET-1 (dose range, 0.96 to 15.36 nmol). MEASUREMENTS: Oxygen saturation, noninvasive BP, and spirometric measurements were made throughout the study visits. Blood was sampled for plasma Ang II levels at baseline and before and after ET-1 inhalation. RESULTS: Ang II infusion did not produce bronchoconstriction per se at either dose prior to ET-1 challenge. Bronchial challenge with inhaled ET-1 produced dose-dependent bronchoconstriction, but there was no difference in bronchial responsiveness to ET-1 comparing infusion of placebo with Ang II at 1 ng/kg/min or 2 ng/kg/min (geometric mean, concentration of ET-1 producing 15% fall, 5.34 nmol, 4.95 nmol, and 4.96 nmol, respectively) (analysis of variance, p > 0.05). There was an increase in systolic and diastolic BP at the higher dose of Ang II compared to placebo (mean 136/86 vs 117/75 mm Hg, respectively). Plasma Ang II was elevated following infusion of both doses of Ang II compared to placebo. CONCLUSIONS: In contrast to the potentiating effect on methacholine-induced bronchoconstriction, Ang II at subbronchoconstrictor doses does not potentiate ET-1-induced bronchoconstriction in asthma.

Smoking and airway inflammation in patients with mild asthma.

STUDY OBJECTIVES: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. DESIGN: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. SETTING: Asthma research unit in a university hospital. PATIENTS OR PARTICIPANTS: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving inhaled or oral steroids at the time of the study. INTERVENTIONS: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. MEASUREMENTS AND RESULTS: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV(1) percent predicted) was negatively related to both sputum IL-8 (r = - 0.52) and sputum neutrophil proportion (r = - 0.38), and sputum IL-8 correlated positively with smoking pack-years (r = 0.57) and percent neutrophil count (r = 0.51). CONCLUSIONS: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics.

Current Perspectives on the Diagnosis and Treatment of Double Depression.

In recent years, the frequency with which patients present with 'double depression', i.e. coexisting chronic depression (dysthymia) and acute major depression, has become increasingly evident. A growing research literature demonstrates that patients with double depression are at increased risk for poor outcome, including poor psychosocial functioning, high usage of medical services, high rates of suicide attempts, and increased recurrence of major depression. Furthermore, naturalistic studies have shown that when these patients are treated in the community, they often do not receive adequate antidepressant medication to treat their acute or chronic depressive disorders.In this article, we introduce a typology that is designed to assist clinicians in determining useful strategies in the short and long term treatment of double depression. This differentiates between those patients with double depression who present primarily with acute depression; those presenting primarily with chronic depression (where treatment can focus on the single, more severe disorder, and may be time-limited or episodic); and those presenting with severe acute depression and severe chronic depression, in whom lifelong medication is often required. Aggressive treatment is recommended for all patients with double depression, but refined treatment strategies based on depressive typology may help to increase compliance, consolidate therapeutic gains and forestall relapse.A growing psychopharmacology literature shows that several different classes of medication [tricyclic antidepressants, monamine oxidase inhibitors, selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors and others] are effective in the treatment of double depression, although perhaps somewhat less effective than in the treatment of acute major depression.