Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness.

BACKGROUND: Partial response, no response, or residual symptoms following antidepressant therapy is common in clinical psychiatry. This study evaluated modafinil in patients with major depressive disorder (MDD) who were partial responders to adequate selective serotonin reuptake inhibitor (SSRI) therapy and excessive sleepiness and fatigue. METHODS: This retrospective analysis pooled the data of patients (18-65 yrs) who participated in two randomized, double-blind, placebo-controlled studies of modafinil (6-week, flexible-dose study of 100-400 mg/day or 8-week, fixed-dose study of 200 mg/day) plus SSRI therapy. Patients (n=348) met criteria for several residual symptoms (Epworth Sleepiness Scale [ESS] score>or=10; 17-item Hamilton Depression Scale [HAM-D] score between 4 and 25; and Fatigue Severity Scale [FSS] score>or=4). RESULTS: Compared to placebo, modafinil augmentation rapidly (within 1 week) and significantly improved overall clinical condition (Clinical Global Impression-Improvement), wakefulness (ESS), depressive symptoms (17-item HAM-D), and fatigue (FSS) (p<.01 for all). At final visit, patients receiving modafinil augmentation experienced statistically significant improvements in overall clinical condition, wakefulness, and depressive symptoms. Modafinil was well tolerated in combination with SSRI. CONCLUSIONS: Results of this pooled analysis provide further evidence suggesting that modafinil is an effective and well-tolerated augmentation therapy for partial responders to SSRI therapy, particularly when patients continue to experience fatigue and excessive sleepiness.     

Tibiotalocalcaneal arthrodesis with retrograde intramedullary nailing

Nineteen patients (20 feet) with severe hindfoot and ankle deformity underwent tibiotalocalcaneal fusion with a retrograde locked intramedullary nail as a limb-salvage procedure. The purpose of this study was to compare the complication rates of this procedure in diabetic versus nondiabetic patients. There were 8 men and 11 women with preoperative diagnoses including Charcot neuroarthropathy, primary osteoarthritis, rheumatoid arthritis, equinocavovarus, posttraumatic osteoarthritis, gouty arthritis, and ankle malunion. Ten of 20 procedures were performed in patients with diabetes. The average patient age was 56 years, and the average postoperative follow-up was 19.8 months. Nineteen of 20 ankles (95%) achieved successful fusion with an average time of 4.1 months. Four patients (21%) required either a fracture brace or an ankle foot orthosis at final follow-up. Five patients (25%) had major complications and 11 patients had minor complications. Major complications included osteomyelitis (n = 2), Charcot arthropathy (n = 2), failure of fixation (n =1), soft-tissue necrosis (n = 1), cardiac arrest (n = 1), cerebral vascular accident (n = 1), and fatal pulmonary embolus (n = 1). All patients with major complications were diabetic, and 14 of 20 combined major and minor complications occurred in patients with diabetes. The complication rate was found to be high in diabetic patients with end-stage deformity undergoing a limb salvage     

Expressed-emotion development and course of schizophrenic illness: considerations based on results of a CFI replication

This study examines the correlation between development of expressed emotion (EE) in relatives and course of illness of 99 DSM-III schizophrenic patients. Patients whose relatives were high EE at baseline and at the 2nd CFI approximately 20 months later had a poor prognosis at the very outset of the study and an unfavourable course of illness. They had a higher rehospitalisation rate, more symptoms, lower psychosocial assessment, and a poorer 2-year and even 8-year outcome. Patients from families with a fluctuating EE or a consistently low EE had better courses. Expessed emotion is therefore a valid predictor not only of symptomatic relapses, but also of other important aspects of schizophrenia. The connection between EE index and course of illness seerns not to be simply reactive or causal, but complex and non-uniform.     

Favorable results of coronary artery bypass grafting in patients older than 75 years

There is controversy whether the short-term and long-term results of coronary artery bypass grafting in elderly patients justify performing the procedure. Between January 1977 and December 1986, 4580 patients underwent coronary artery bypass grafting, of whom 222 (4.9%) were 75 years old or older (mean 77 years). There were 143 men and 79 women and 139 (63%) were in New York Heart Association class IV. One hundred forty-six patients (66%) had had at least one preoperative myocardial infarction. Myocardial revascularization was performed under emergency conditions in 17 patients (18%). The mammary artery was used in 43%, 96% of the patients received two or more grafts. The mean number of bypass grafts was 3.1 per patient. The overall hospital mortality rate was 10.8% (24/222), 3.6% for elective procedures, 14.9% in urgent cases, and 35% in emergencies. In contrast, the overall early mortality rate was 3.1% in 4358 patients less than 75 years old. Complications occurred in 83 patients (37%). Of the patients discharged from the hospital, 198 were followed up for a mean of 48 months (1 to 130). Actuarial probability of survival was 75% at 48 months. Postoperatively 70% were in New York Heart Association class I or II and only 21% were rehospitalized for cardiac problems. During the follow-up period 77% of the patients were free from angina, and of those experiencing angina the mean time from operation to the first episode was 75 months. Although elderly patients have a somewhat increased operative mortality rate, particularly if operated on urgently or emergently, long-term survival and freedom from angina are excellent and justify continued performance of coronary bypass grafting in selected patients over 75 years of age.     

Twenty-four-hour ambulatory blood pressure profiles in pediatric patients after renal transplantation

Ambulatory blood pressure monitoring was applied in 27 pediatric patients aged 6.3 – 24.3 (median 15.0) years who had been transplanted 1.5 – 8.4 years previously. Daytime values were compared with the mean of 10 concomitant casual blood pressure recordings. At the time of the study, antihypertensive drugs were given to 17 patients. Inulin clearance ranged from 18 to 116 (median 66) ml/min per 1.73 m². Ambulatory blood pressure monitoring confirmed hypertension or normotension determined by casual blood pressure measurements in 63% of patients. The physiological nocturnal dip in blood pressure was attenuated or reversed in 8 of 27 patients. It was reduced in all 3 patients with renal artery stenosis of the graft, in 3 of 4 patients with chronic rejection, in the only patient with recurrent focal segmental glomerulosclerosis, and in 1 of 6 patients with past acute rejection. The dipping was not related to inulin clearance. In conclusion, casual blood pressure measurements do not accurately reflect blood pressure in pediatric patients transplanted more than 1.5 years previously. A reduced nocturnal dip in blood pressure may indicate an underlying renovascular or renoparenchymal pathology. Ambulatory blood pressure monitoring should regularly be applied in patients with renal transplants. Received May 23, 1995; received in revised form June 18, 1996; accepted June 20, 1996     

Group A Streptococcus invasive infections: a review

The incidence of group A Streptococcus (GAS) invasive infections has been increasing worldwide, and there is no obvious explanation for this phenomenon. In 1993, a working group on severe GAS infections was established to define accurately what constitutes an invasive infection. Three types of infection are particularly feared: necrotizing fasciitis, myositis and a newly defined entity, named streptococcal toxic shock syndrome (STSS) because of a certain analogy with its staphylococcal counterpart. GAS produces many toxins responsible for its clinical manifestations. Some of them, labelled streptococcal pyrogenic exotoxins, have been characterized as superantigens. These proteins play a key role in initiating the immune response to GAS and are mostly responsible for the precipitous course of invasive infections. Death rates are high in streptococcal invasive infections, ranging from about 20% for necrotizing fasciitis to almost 100% for myositis. Therapy consists mainly of high doses of antibiotic combinations, aggressive surgery, and intravenous administration of immunoglobulins for STSS.     

Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

In vitro evaluation of ablation parameters of normal and fibrous aorta using smooth excimer laser coronary angioplasty

A modified exeimer laser energy delivery system was used to irradiate 100 segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8 fiber bundles consisting of 50 fibers each resulting in a reduction of the applied pulse energy. The total repetition rate was increased to 150 Hz in order to keep the repetition rate per fiber bundle close to 20 Hz and to minimize thermal injury. The results demonstrate that effective ablation (etch rate per 8 pulses > 2.0 μm) occurred at an energy fluency of 50 mJ/mm² in both normal and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures, cracks, and vacuolization) was in a range of 100 ± 28 to 152 ± 30 μm for normal aorta and in a range of 57 ± 35 to 110 ± 39 μm for fibrous aorta. We conclude that effective ablation of normal and fibrous human aorta can be achieved by the application of smooth excimer laser coronary angioplasty. This improvement of excimer laser technology may result in a reduction of shock wave- and cavitation-induced damage leading to a reduction of tissue injury. However, this awaits further in vitro and in vivo confirmation. © 1993 Wiley-Liss, Inc.     

Self-inflicted orbital and intracranial injury with a retained foreign body, associated with psychotic depression: Case report and review

Reports of intracranial self-multilation by psychotic individuals are associated with severe mental disorders, criminality, or both. We describe a psychotically depressed male who drove a ballpoint pen through his right medial canthus and into his intracranial compartment. The patient developed a cavernous sinus syndrome and a traumatic dissection of the cavernous portion of the carotid artery. The pen was removed intraoperatively. Postoperatively, the patient was placed on a course of broad-spectrum antibiotics, antidepressants, and antipsychotic medications, and he has received long-term psychiatric follow-up. The literature related to these unusual cases is reviewed, and relevant surgical, medical, and psychiatric aspects of treatment are discussed.