Psychiatric syncope: a new look at an old disease

Psychiatric disorders in patients with unexplained syncope or presyncope have received little attention in the recent medical literature. Seventy-two patients with unexplained syncope and presyncope referred to the Duke Syncope Clinic received a standardized evaluation. Symptoms appeared to be explained by a psychiatric diagnosis in 17 (24%) patients (panic disorder in 13%, and major depression in 11%). These patients were younger than other patients with syncope and presyncope (p less than .001) and had more disability due to their syncope and presyncope (p less than .01). They also had more frequent episodes of syncope (p less than .005) and more symptoms as a part of their prodrome (p less than .0001). Treatment aimed at the psychiatric diagnosis resulted in a remission from syncopal or presyncopal symptoms in 90% of patients who complied with therapy. The authors conclude that psychiatric disorders are common in patients with syncope and presyncope, that certain characteristics of the patient and prodrome may alert physicians to a psychiatric diagnosis, and that directed treatment may result in relief from symptoms.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

Vertebral osteomyelitis with a rare etiology diagnosed by fine‐needle aspiration cytology

Invasive fungal infections are rare in immunocompromised individuals, but are not uncommon in immunologically compromised patients. Bone involvement by these infections, though exceedingly rare, may occur due to direct extension of the infection from a neighboring organ or due to hematogenous dissemination in critically ill patients. Still rarer is the invasive aspergillosis involving either the vertebral body or the intervertebral disc with extension into the extradural space as an abscess. We report one such case of vertebral osteomyelitis due to Aspergillus diagnosed by FNAC in a well‐controlled diabetic patient who presented with nonspecific symptoms and in whom a clinical and radiological diagnosis of Pott's spine was considered. The present case stresses the importance of early cytologic diagnosis of vertebral Aspergillus osteomyelitis, which in conjunction with appropriate timely medical and surgical treatment, offers good recovery without much sequelae or threat to life. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

The efficacy of amino acid-based formulas in relieving the symptoms of cow''s milk allergy: a systematic review

The aim of this systematic review was to evaluate the efficacy of amino acid-based formulas (AAF) in patients with cow's milk allergy (CMA). Studies were identified using electronic databases and bibliography searches. Subjects eligible for inclusion were patients of any age with CMA or symptoms suggestive of it. Comparisons of interest were AAF vs. extensively hydrolysed formula (eHF), AAF vs. soy-based formula (SF) and AAF vs. cow's milk or cow's milk-based formula. Outcomes of interest were gastrointestinal (GI), dermatological, respiratory and behavioural symptoms as well as growth. A total of 20 studies [three head-to-head randomized controlled trials (RCTs), three cross-over challenge RCTs, seven clinical trials (CTs) and seven case reports (CRs)] were included in the review. In infants with confirmed or suspected CMA, the use of an AAF was shown to be safe and efficacious. Findings from RCT comparisons of AAF with eHF showed that both formulas are equally efficacious at relieving the symptoms of CMA in confirmed or suspected cases. However, infants in specific subgroups (e.g. non-IgE mediated food-induced gastro-enterocolitis-proctitis syndromes with failure to thrive, severe atopic eczema, or with symptoms during exclusive breastfeeding) were more likely overall to benefit from AAF, as intolerance to eHF may occur. In such cases, symptoms persisting despite eHF feeding usually remit on AAF, and catch-up growth may be seen. Meta-analysis of the findings was not possible due to lack of homogenous reporting of outcomes in the original trials. This systematic review shows clinical benefit from use of AAF in both symptoms and growth in infants and children with CMA who fail to tolerate eHF. Further studies are required to determine the relative medical or economic value of initial treatment with AAF in infants at high risk of eHF intolerance.     

A prostaglandin theory of neuroleptic malignant syndrome

A subgroup of patients with schizophrenia or other psychoses may have an increased PGE receptor sensitivity in the brain, which may be due to low levels of PGE. Some of these patients may develop a severe dopaminergic blockade when given neuroleptics which stimulate PGE synthesis. This may lead to the symptoms of neuroleptic malignant syndrome. Calcium channel blockers inhibit the prostaglandin output caused by norepinephrine and these agents may prove useful in the treatment of neuroleptic malignant syndrome.     

Renal splenic heterotopia,a rare mimic of renal neoplasia: Case report of imaging and fine-needle aspiration biopsy

Renal splenic heterotopia, a very rare benign occurrence of splenic tissue within the renal capsule, mimics organizing capsular hemorrhage, adenomyolipoma and renal cortical adenoma or carcinoma. It is found incidentally as a result of imaging assymptomatic kidneys for other reasons or may cause signs and symptoms due to mass effect and hypersplenism. When occurring in patients who had had splenectomy it has been classified as splenosis. When found in patients with intact spleens it is called splenorenal fusion and considered to be a developmental heterotopia. Renal splenic heterotopia can be diagnosed by 99mTc-sulfur colloid scan and confirmed with fine needle aspiration biopsy cell block preparations. Unnecessary nephrectomy can be avoided if splenic heterotopia is included in the differential diagnosis of renal lesions, particularly in splenectomized patients.     

Current status of augmentation and combination treatments for major depressive disorder: a literature review and a proposal for a novel approach to improve practice

Most patients with major depressive disorder (MDD) do not reach symptom remission. These patients with residual symptoms have worse function and worse prognosis than those who remit. Several augmentation and combination treatments are used to either increase the chances of achieving remission or to eliminate/minimize residual depressive symptoms. Evidence for these pharmacological approaches rests primarily on open, uncontrolled studies, and there are clearly not enough controlled studies. Clinicians should carefully weigh these different treatment options to increase their patients' chances of achieving and sustaining remission from depression. This paper will review the pertinent studies and will propose a novel approach to improve practice involving the use of augmentation or combination strategies at the outset of initial treatment to primarily enhance the chances of remission through synergy and/or a broader spectrum of action. This novel approach could potentially enhance retention and/or increase remission rates since the lack of response with antidepressant monotherapy may lead many depressed patients with little or no benefit to drop out of treatment, precluding the subsequent use of augmentation or combination strategies altogether. In addition, the emergence of certain side-effects (e.g., agitation, insomnia) or the persistence of some initial baseline symptoms (e.g., anxiety, insomnia) may lead to premature discontinuation from monotherapy in the absence of concomitant use of augmenting pharmacological options targeting these symptoms.     

Clinical outcomes of ABO-incompatible RBC transfusions

Factors that predict outcome after ABO-incompatible RBC transfusions are not well defined. We studied whether the volume of incompatible blood transfused would determine the signs and symptoms and survival outcome for ABO-incompatible RBC transfusions. We reviewed ABO-incompatible RBC transfusions from our institutions and our consultations for 35 years and from a survey of America's Blood Centers' members regarding causes, volume, signs, symptoms, and outcomes of ABO-incompatible RBC transfusions in their service areas from 1995 through 2005.All ABO-incompatible transfusions were due to error; 26 (62%) of 42 occurred at the patient's bedside. Of 36 patients who received more than 50 mL of incompatible blood, 23 (64%) manifested signs or symptoms related to the incompatible transfusion, and 6 (17)% died. Only 3 (25%) of 12 patients who received 50 mL or less of incompatible blood had associated signs or symptoms, and none died. Hypotension, hemoglobinuria, and/or hemoglobinemia were the most frequent findings in survivors and patients who died.ABO-incompatible RBC transfusion does not inevitably mean death or even occurrence of symptoms. Prompt recognition and discontinuation of the transfusion are critical because transfusing less ABO-incompatible blood may minimize signs and symptoms and may prevent death.     

Endovascular stenting as a first choice for the palliation of superior vena cava syndrome

To assess the effectiveness of endovascular stenting for the palliation of superior vena cava (SVC) syndrome, endovascular stent insertion was attempted in 10 patients with symptomatic occlusion of the SVC. All the patients had known malignant disease of the thorax. Eight patients had been treated previously with chemotherapy and radiotherapy (n=5), chemotherapy alone (n=2), or pneumonectomy and radiotherapy (n=1). After developing SVC syndrome, all the patients were stented before receiving any other treatment. After single or multiple endovascular stents were inserted, five of eight patients were treated with chemotherapy and radiotherapy (n=2) or chemotherapy alone (n=3). Resolution of symptoms was achieved in nine patients within 72 hr (90%). In one patient, the symptoms did not disappear until a second intervention. At follow up, symptoms had recurred in two of ten patients (20%) after intervals of 15 and 60 days. Five patients have died from their cancers, although they remained free of symptoms of SVC occlusion until death. In conclusion, endovascular stent insertion is an effective treatment for palliation of SVC syndrome. Endovascular stent insertion can be considered the first choice of treatment, due to the immediate relief of symptoms and excellent sustained symptomatic relief.     

Stereotyped responding by schizophrenic patients on a two-choice guessing task

On each of a sequence of trials subjects had to guess whether a cross would appear on the left or the right side of a computer screen. The sequence of cross positions was random. Normal controls, manic-depressive patients and patients with senile dementia produced relatively random sequences of responses, as did acute schizophrenic patients with positive symptoms. Acute schizophrenic patients with negative symptoms and chronic patients produced more stereotyped sequences with many response alternations (LRLR). Chronic schizophrenic patients with negative symptoms and intellectual deterioration (defect state) produced very stereotyped sequences with many preservations (LLLL). This severe restriction of response sequences is similar to that shown by animals after treatment with amphetamine. It is suggested that it is due to an impairment of a higher order control process which normally inhibits the repetition of sequences of behaviour when these have proved inappropriate.     

Psychogenic explanation of symptoms as a denial of physical illness

Few reports have been published of patients explaining their symptoms as “psychogenic” in order to defend against the recognition of potentially threatening physical illness. With increasing public sophistication and awareness that emotional problems can cause somatic symptoms, such cases may become more common. The author reports on four physically ill patients who considered their symptoms psychogenic. They used denial, rationalization, and displacement to avoid recognizing the physical nature of their disorders. Family members’ reactions rein-forced their distorted perceptions. Careful psychiatric interviewing with supportive confrontation facilitated a therapeutic alliance, and the patients all achieved or approached acceptance of their correct diagnoses.     

Sensory hyperreactivity – a possible mechanism underlying cough and asthma-like symptoms

Background Investigations of patients referred for suspected asthma have revealed a little-known group with symptoms suggesting hyperreactive airways in whom provocation with methacholine does not lead to bronchial obstruction. The underlying mechanisms are not known, and no objective diagnostic method has been available.
Methods Provocations by inhalation of capsaicin solutions in stepwise increasing concentrations were used. Ten patients with asthma-like symptoms after exposure to nonspecific irritating stimuli, but without IgE-mediated allergy or demonstrable bronchial obstruction, were compared to 10 patients with verified bronchial asthma and 28 healthy controls. Results The patients with asthma-like symptoms reacted with cough in a dose-dependent way. The number of coughs was significantly greater than in asthmatic patients and healthy controls. The latter two groups did not differ significantly.
Conclusions The capsaicin provocation test may be a valuable method for showing not only a greater cough sensitivity, but also asthma-like symptoms. The pathophysiology underlying the symptoms may be related to increased sensitivity of free, overactive nerve endings in the respiratory mucosa. Therefore, we suggest that this overreaction in the lower airways be called "sensory hyperreactivity".     

Further evidence of the increased risk for malignant peripheral nerve sheath tumour from a Scottish cohort of patients with neurofibromatosis type 1

A recent study, looking at the lifetime risk of developing malignant peripheral nerve sheath tumour (MPNST) in patients with neurofibromatosis type 1 (NF1), estimated the risk to be 8-13%. Prior to this, longitudinal studies had shown that patients with NF1 had a risk of 4-5% of developing MPNST, and cross-sectional studies had found that only 1-2% of patients with NF1 had MPNST. The aim of this study was to estimate the lifetime risk of MPNST in patients with NF1 in southern Scotland, using patient records obtained from the Edinburgh and Glasgow Genetic Units and Scottish Cancer Register. In the period 1993-2002, 14 patients with NF1 were diagnosed with MPNST in a population of 3.5 million. The lifetime risk of MPNST in the Scottish patients with NF1 was calculated to be 5.9-10.3%. This provides further evidence that patients with NF1 are at greater risk of developing MPNST than was previously estimated, and emphasises the importance of educating patients about suspicious symptoms, which may need an urgent medical opinion. The mean age at diagnosis of MPNST (p<0.05) and 5-year survival (p<0.01) were significantly lower in patients with NF1 than in unaffected individuals. This may be due to patients with NF1 presenting later, because the tumour is mistaken for a neurofibroma, or due to MPNST having a more aggressive course in NF1.     

Chronic Diarrhea in Common Variable Immunodeficiency: a Case Series and Review of the Literature

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition. We describe three female CVID adult patients presenting with chronic diarrhea, weight loss, and protein-energy malnutrition due to different underlying conditions. Our review of the literature explores the various gastrointestinal involvements in CVID and points out several histopathological findings proper of the disease, thus highlighting the relevance of the endoscopic and histological assessment in CVID patients presenting with chronic diarrhea.     

Assessing the community prevalence of bipolar spectrum symptoms by the mood disorder questionnaire

BACKGROUND: The goal of this study was to assess the frequency and spectrum of symptoms related to bipolar disorders in a community sample by means of a self-rating questionnaire. METHOD: The Mood Disorder Questionnaire, a self-rating scale which evaluates DSM-IV manic/hypomanic symptoms, was administered to a community sample of 1,034 individuals recruited through advertisements. Symptom interrelationships were studied by factor analysis. RESULTS: 275 individuals (26.6%) reported moderate or severe impairment due to the symptoms. Manic/hypomanic symptoms were present in a high proportion of individuals. Factor analysis found a two-factor structure of bipolar spectrum symptoms (an elevated mood overactivity factor, and an irritable behavior factor). CONCLUSION: The findings of this study highlight the need of complementing clinical investigations on the bipolar spectrum with community studies. Subclinical manic-hypomanic symptoms may be present also in allegedly unipolar patients and may have implications on the course of illness.     

Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue

We studied the effects of a long-acting analogue of somatostatin (SMS 201-995, Sandoz) in 25 patients with histologically proved metastatic carcinoid tumors and the carcinoid syndrome. This drug was self-administered by subcutaneous injection at a dose of 150 micrograms three times daily. Flushing and diarrhea associated with the syndrome were promptly relieved in 22 patients. All 25 patients had an elevated 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) (mean, 265 mg per 24 hours; range, 14 to 1079), which served as an objective indicator of disease activity. Eighteen of the 25 patients (72 percent) had a decrease of 50 percent or more in their urinary 5-HIAA levels, as compared with the pretreatment values. The median duration of this biochemical response was more than 12 months (range, 1 to greater than 18). Since no serious toxicity was observed, we conclude that SMS 201-995 may be appropriate for use as early therapy in patients with symptoms due to the carcinoid syndrome who have not responded to simpler measures.     

Personality and symptom sensitivity predictors of alprazolam withdrawal in panic disorder

BACKGROUND: Discontinuation of benzodiazepine (BZ) treatment results in a well-characterized withdrawal syndrome in 40-50% of anxious patients. While numerous studies have established the role of BZ dose, treatment duration, half-life, potency, rate of withdrawal and severity of underling anxiety disorder in predicting severity of withdrawal symptoms, fewer studies have examined the role of psychological and personality factors. METHOD: In 123 panic disorder patients undergoing gradual tapered discontinuation of alprazolam in conjunction with pre-treatment with carbamazepine or placebo, the relationship between measures of 'symptom sensitivity' and 'harm avoidance', and severity of withdrawal symptoms measured as peak severity of symptoms, time before taper needed to be slowed due to symptoms, and ability to complete taper, was examined. RESULTS: After controlling for the less substantial effects of dose, treatment duration, pre-taper anxiety and panic attack frequency, measures of symptom sensitivity and harm avoidance accounted for an additional 3-6% of withdrawal variance. CONCLUSIONS: These results show an effect of symptom sensitivity and harm avoidance on BZ withdrawal symptoms, comparable to prior findings linking dependent personality characteristics to withdrawal severity. Failure to show the expected effect on ability to complete taper may be due to either the more symptomatic nature of the patients in this study.     

Is treatment-associated hypomania rare with duloxetine: secondary analysis of controlled trials in non-bipolar depression

BACKGROUND: Selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitors (SNRIs) like duloxetine have the efficacy of tricyclic antidepressants (TCAs) with a more tolerable side-effect profile. Bipolar disorder is often undetected, with the most common misdiagnosis being unipolar depression. Studies have suggested that treatment of bipolar and unipolar depression with heterocyclic TCAs may increase the risk of switch rate to mania. Studies of antidepressants in unipolar major depression show a small risk of mania or hypomania, presumably because some bipolar depressives were mistakenly studied. This study investigated the rate of hypomania, mania, and hypomanic-like symptoms observed during treatment with duloxetine in patients with major depression. METHODS: This was a retrospective analysis of data from eight placebo-controlled, double-blind, randomized clinical trials of duloxetine in patients with non-bipolar major depression. LIMITATIONS: The studies were of limited duration. Manic or hypomanic symptoms were not elicited using standardized mania rating scale instruments. RESULTS: One case of mania occurred in the placebo group (0.1%), and two cases of hypomania were observed in the duloxetine-treated group (0.2%). Among hypomanic-like symptoms, only insomnia was significantly higher in the duloxetine group than in the placebo group (p<0.05). CONCLUSIONS: Duloxetine was associated with a low incidence of treatment-emergent hypomania, mania, or hypomanic-like symptoms in patients with major depressive disorder (MDD). The low incidence reported here may be due to greater diagnostic diligence on the part of the investigators. It is possible that the cases reported likely reflect inclusion of misdiagnosed bipolar II patients rather than true unipolar MDD cases. The effect of duloxetine in patients with bipolar depression is not known.     

Double-blind trial comparing flunisolide and placebo for the treatment of perennial rhinitis

The effectiveness of a new topical steroid, flunisolide, was evaluated for the treatment of patients with perennial rhinitis. The sixty-nine patients in this 8 week double-blind parallel trial received either 300 γg/day of flunisolide or placebo. The flunisolide group showed statistically greater improvement than the placebo group in such symptoms as the duration of sneezing, stuffy nose, runny nose and nose blowing. 63% of the flunisolide group compared with 39% of the placebo group felt the test spray had provided substantial or total control of their nasal symptoms (P= 0·0026). When those patients who were skin test-positive (allergic) were considered separately from those who were skin test-negative (non-allergic), differences in responsiveness were noted. While those patients who had negative skin tests received greater relief of their symptoms with flunisolide than with placebo, patients who had positive skin tests showed a greater responsiveness to flunisolide and reported a higher incidence of significant or total control of their symptoms. Careful monitoring of plasma cortisol levels revealed no evidence of adrenal suppression in any of the patients in this trial. This lack of suppression may be due to two factors: (a) flunisolide is rapidly metabolized into a metabolite with a low degree of activity and (b) a very low dose of corticosteroid is administered.