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Purpose: The effectiveness and tolerability of switching patients' therapy from brand-name to generic clozapine are reviewed., Summary: Clozapine is the most effective treatment for patients with refractory psychotic disorders and is also effective for reducing suicidal and violent behavior in this same population. Generic versions of clozapine are widely used. However, possible differences in pharmacokinetic profiles between branded and generic clozapine, and the potential risks of medication changes in severely ill but stable patients, may result in apprehension about converting from branded to generic clozapine. Articles, abstracts, and clinical presentations that compared clinical outcomes between Clozaril (Novartis Pharmaceuticals, East Hanover, NJ) and generic forms of clozapine in patients with primary psychotic disorders, bipolar disorder, or related conditions were identified via a computerized search of the medical literature. Thirteen relevant reports, mostly uncontrolled observational studies or chart reviews, described the effects of switching from brand-name to generic clozapine in 966 patients. The majority of patients tolerated conversion without worsening of symptoms or adverse effects, increased intensive service utilization, or medication adjustment. Clinical deterioration was described in a case review and in one randomized, controlled study., Conclusion: Available literature supports the effectiveness and safety of generic clozapine formulations in patients who previously were stable during treatment with brand-name clozapine. The risk of poor outcome after conversion to a generic clozapine formulation appears to be low but difficult to predict. Patients should be closely monitored during the first one to three months after conversion from one formulation to another.

Objective: To assess the outcome of patient education after splenectomy and vaccination and to determine the safety and efficacy of pneumococcal revaccination 2 or more years after primary vaccination., Main Outcome Measures: Titers to serotype no. 6 and no. 23 pneumococcus and cutaneous and systemic reaction to revaccination., Results: A total of 112 consecutive postsplenectomy patients receiving pneumococcal vaccine were identified; 45 were contacted and offered revaccination; 24 patients demonstrated a lack of understanding of the postsplenectomy state (unaware of splenectomy n = 2, unaware of splenectomy risk n = 8, unaware of vaccine n = 23); 3 patients had infections requiring hospitalization (pneumonia, strep throat and tonsillitis, pneumonia and bacteremia); 40 patients agreed to revaccination, and 33 patients returned for follow-up titers; 16 of 33 (48%) demonstrated at least a two-fold increase in at least one titer. Only 15% described the revaccination as worse than a tetanus shot., Conclusions: (1) Despite physician-patient conversations, pamphlets, and Medic Alert bracelets, patient retention was poor. (2) All splenectomy patients should be revaccinated and reeducated between two and six years after splenectomy. (3) Revaccination after two years was well tolerated. (4) There were no fatal episodes of pneumococcal sepsis in over 200 patient years.

The aim of this study was to determine the relationship of the white blood cell (WBC) count to bacteraemia, and the risk of bacteraemia after splenectomy. The case series study was carried out at the Vanderbilt University Level I Trauma Center, and included 11,870 consecutive trauma admissions: 258 required a splenectomy (191) or splenorrhaphy (67). Bacteraemia was defined as the presence of a positive blood culture. Statistical analysis included ANOVA, the non-parametric Kruskal-Wallis test and logistical regression. Forty-two (22 per cent) of the splenectomy patients had positive blood cultures, while only six (9 per cent) of the splenorrhaphy patients had positive cultures. For the group of patients requiring a splenectomy, the mean WBC count was higher and more persistent in patients with bacteraemia. Logistical regression demonstrated that the type of surgery does not significantly correlate with bacteraemia after accounting for severity of injury (TRISS). The study conclusions were as follows (1) for the group of patients with bacteraemia after splenectomy, the peak WBC count was higher and more persistent than that which occurred in the group of patients without bacteraemia after splenectomy; (2) the WBC count cannot be used to predict bacteraemia for an individual patient, but a WBC count greater than 20,000 after 10 days should initiate a vigorous search for infection; (3) the severity of injury (and not splenectomy/splenorrhaphy) accounted for the increased risk of bacteraemia in population studied.

Aztreonam represents the first synthetic monobactam marketed in the United States and is being viewed as a nontoxic alternative to the aminoglycosides. Advantages of aztreonam over the aminoglycosides include lack of ototoxicity and nephrotoxicity and better penetration into the CSF. Additional advantages include its use in penicillin and cephalosporin allergic patients. Disadvantages of aztreonam compared to the aminoglycosides include the cost of the drug (50 times more expensive than gentamicin), the lack of post antibiotic effect, resistance to P. aeruginosa, and lack of significant activity against Enterobacter cloacae and E. aerogenes. There are insufficient clinical trials to document the superiority of aztreonam over the "gold standard" therapy for gram-negative infections--the aminoglycosides. The restricted anti-microbial spectrum of aztreonam has been proposed as an advantage. Theoretically, this would permit targeting of a gram-negative pathogen with minimal disruption of the (largely anaerobic) intestinal flora. In fact, use of this drug has been associated with colonization of gram-positive organism, especially enterococci. Although aztreonam appears to be an excellent antibiotic, its use has been limited by its relatively high cost, narrow spectrum of activity, and the availability of numerous alternative agents.

Recombinant human erythropoietin (r-HuEPO) administration to a Jehovah's witness refusing blood transfusions increased her nadir packed cell volume from 13% to 37% and reticulocyte count from 2% to 17.7%. R-HuEPO may provide an alternative safe and effective therapy in life-threatening anemia when blood transfusions are unacceptable to the patient.

Transient hypotension may be one of many factors contributing to the high prevalence of falls among elderly people. To determine the frequency and magnitude of hypotensive responses to common daily activities, and their potential relationship to falls in the elderly, we examined blood pressure (BP) and heart rate during a standardized series of activities in 38 institutionalized recurrent fallers (age, 87 +/- 6 years), 20 institutionalized nonfallers (age, 85 +/- 5 years), and 10 healthy young control subjects (age, 24 +/- 3 years). The coefficient of variation for systolic BP during all activities was higher in elderly subjects (fallers, 14% +/- 5%; nonfallers, 12% +/- 3%) than in young control subjects (8% +/- 1%). In contrast, the coefficient of variation for heart rate during all activities was higher in young subjects than in the elderly subjects. Elderly subjects had marked BP reduction following meals and nitroglycerin, which was significantly greater in fallers than in nonfallers, independent of the cause of the fall. Thus, institutionalized elderly have marked BP variability and hypotensive responses to meals and nitroglycerin. A decline in BP during common preload-reducing stresses may predispose some elderly people to falls.

Clinical studies of syncope suggest a decreased prevalence of vasovagal syncope in old age. To examine this possibility and its pathophysiologic implications, we report the results of two studies. The first evaluated responses to head-up tilt in young and old subjects. Presyncopal vasovagal symptoms occurred in 4 of 9 young subjects and only 1 of 22 old subjects. The second study asked whether decreased beta-adrenergic responsiveness protected the old during tilt via unopposed alpha-adrenergic-mediated vasoconstriction. Blood pressure, heart rate, and forearm vascular resistance responses to tilt in 11 healthy young subjects randomized to receive intravenous propranolol hydrochloride or saline were compared with those of 10 healthy elderly. Propranolol attenuated heart rate and forearm vascular resistance responses. Vasovagal symptoms occurred in 4 young and no old subjects; 2 were symptomatic during propranolol administration. Thus, presyncopal vasovagal symptoms are less common during tilt in old age. Propranolol did not prevent the vasovagal reaction or enhance forearm vasoconstriction. Propranolol's attenuation of vasoconstriction may be due to decreased activation of cardiopulmonary baroreceptors during beta-blockade.

We present a case of a 55-year-old woman requiring prolonged therapy with intravenous isoniazid and rifampin secondary to extensive bowel disease. We believe that this is the first U.S. report of a patient receiving both medications by the iv route. After months of therapy the patient has not experienced side effects secondary to this route of administration. We believe that iv isoniazid and rifampin provides a safe alternative method of delivery when clinical situations dictate this route.