A deadly prescription: combination of methotrexate and trimethoprim-sulfamethoxazole.

Methotrexate (MTX) is a chemotherapeutic synthetic(s) phase cell cycle inhibitor, and its role has evolved as an immunological agent in autoimmune diseases like rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, etc. Trimethoprim-sulfamethoxazole (TS) is one of the most widely prescribed antibiotics commonly used for urinary tract infections, exacerbations of chronic bronchitis, traveler's diarrhea, and pneumocystis pneumonia. Both MTX and TS can have significantly overlapping side effects involving dermatologic, renal, and hematological systems, and the combination of these can be deadly. Our case is about the combination of MTX and TS that leads to mucocutaneous ulceration, leukopenia, and renal insufficiency. The purpose of this case is to increase awareness of potentially significant toxicity from the combination of MTX with TS. Abbreviations: MTX: methotrexate; TS: trimethoprim-sulfamethoxazole; ED: emergency department; IV: intravenous; GI: gastrointestinal; NSAIDs: nonsteroidal anti-inflammatory drugs.

Some neck swellings are serious; a case of Lemierre's Syndrome.

Lemierre's syndrome also termed post-anginal septicemia, is a disease characterized by internal jugular septic thrombophlebitis leading to Fusobacterium septicemia with multiple metastatic foci following an oropharyngeal infection. Diagnosis and management is challenging and can result in fatal consequences due to potential multisystem involvement and multiple complications. We describe here a case of Lemierre's syndrome with multifocal pneumonia, acute renal failure and protracted course of illness over forty days with successful recovery. A brief overview of literature is also presented.

Effects of lung volume reduction surgery on sleep quality and nocturnal gas exchange in patients with severe emphysema.

STUDY OBJECTIVES: We hypothesized that associated with improvements in respiratory mechanics, lung volume reduction surgery (LVRS) would result in an improvement in both sleep quality and nocturnal oxygenation in patients with severe emphysema. DESIGN: Prospective randomized controlled trial. SETTING: University hospital. PATIENTS: Sixteen patients (10 men, 63 +/- 6 years [+/- SD]) with severe airflow limitation (FEV(1), 28 +/- 10% predicted) and hyperinflation (total lung capacity, 123 +/- 14% predicted) who were part of the National Emphysema Treatment Trial. INTERVENTIONS AND MEASUREMENTS: Patients completed 6 to 10 weeks of outpatient pulmonary rehabilitation. Spirometry, measurement of lung volumes, arterial blood gas analysis, and polysomnography were performed prior to randomization and again 6 months after therapy. Ten patients underwent LVRS and optimal medical therapy, while 6 patients received optimal medical therapy only. RESULTS: Total sleep time and sleep efficiency improved following LVRS (from 184 +/- 111 to 272 +/- 126 min [p = 0.007], and from 45 +/- 26 to 61 +/- 26% [p = 0.01], respectively), while there was no change with medical therapy alone (236 +/- 75 to 211 +/- 125 min [p = 0.8], and from 60 +/- 18 to 52 +/- 17% [p = 0.5], respectively). The mean and lowest oxygen saturation during the night improved with LVRS (from 90 +/- 7 to 93 +/- 4% [p = 0.05], and from 83 +/- 10 to 86 +/- 10% [p = 0.03], respectively), while no change was noted in the medical therapy group (from 91 +/- 5 to 91 +/- 5 [p = 1.0], and from 84 +/- 5 to 82 +/- 6% [p = 0.3], respectively). There was a correlation between the change in FEV(1) and change in the lowest oxygen saturation during the night (r = 0.6, p = 0.02). In addition, there was an inverse correlation between the change in the lowest oxygen saturation during the night and the change in residual volume (- r = 0.5, p = 0.04) and functional residual capacity (- r = 0.6, p = 0.03). CONCLUSION: In patients with severe emphysema, LVRS, but not continued optimal medical therapy, results in improved sleep quality and nocturnal oxygenation. Improvements in nocturnal oxygenation correlate with improved airflow and a decrease in hyperinflation and air trapping.

Effects of nasal continuous positive airway pressure on oxygen body stores in patients with Cheyne-Stokes respiration and congestive heart failure.

STUDY OBJECTIVES: The mechanism(s) by which nasal continuous positive airway pressure (CPAP) is effective in the treatment of Cheyne-Stokes respiration (CSR) in patients with congestive heart failure (CHF) remains uncertain, and may involve an increase in total oxygen body stores (dampening), changes in central and peripheral controller gain, and/or improvement in cardiac function. The purpose of this study was to evaluate the effects of nasal CPAP on total oxygen stores, as measured by the rate of fall of arterial oxyhemoglobin saturation (dSaO(2)/dt), to determine if dampening may play a role in the attenuation of CSR in patients with CHF. DESIGN: Prospective controlled trial. SETTING: University hospital. PATIENTS: Nine male patients (mean +/- SD age, 59 +/- 8 years) with CHF and a mean left ventricular ejection fraction (LVEF) of 16 +/- 4%. INTERVENTIONS AND MEASUREMENTS: All patients had known CSR, as identified on a baseline polysomnographic study. Patients then underwent repeat polysomnography while receiving nasal CPAP (9 +/- 0.3 cm H(2)O). The polysomnography consisted of recording of breathing pattern, pulse oximetry, and EEG. dSaO(2)/dt was measured as the slope of a line drawn adjacent to the falling linear portion of the arterial oxygen saturation (SaO(2)) curve associated with a central apnea. All patients underwent echocardiography and right-heart catheterization within 1 month of the study to measure LVEF and cardiac hemodynamics, respectively. RESULTS: There was a significant decrease in the apnea-hypopnea index (AHI) with nasal CPAP, from 44 +/- 27 events per hour at baseline to 15 +/- 24 events per hour with nasal CPAP (p = 0.004). When compared to baseline, dSaO(2)/dt significantly decreased with nasal CPAP from 0.42 +/- 0.15% to 0.20 +/- 0.07%/s (p < 0.001). The postapneic SaO(2), when compared to baseline, significantly increased with nasal CPAP, from 87 +/- 5% to 91 +/- 4% (p < 0.05). The preapneic SaO(2) did not significantly change, from a baseline of 96 +/- 2% to 96 +/- 3% with nasal CPAP (p = 0.8). When compared to baseline, the apnea duration and heart rate did not change with nasal CPAP. While there was a significant correlation noted between baseline postapneic SaO(2) and dSaO(2)/dt (r = 0.8, p = 0.02), no correlation was seen between baseline preapneic SaO(2) and dSaO(2)/dt (r = 0.1, p = 0.7). A significant correlation was noted between baseline dSaO(2)/dt and the AHI (r = 0.7, p = 0.02). With CPAP, there was a significant correlation noted between dSaO(2)/dt and the AHI (R = 0.7, p = 0.04), but no correlation was noted between dSaO(2)/dt and postapneic SaO(2) (R = 0.1, p = 0.8). CONCLUSION: Nasal CPAP significantly decreases dSaO(2)/dt and thus increases total body oxygen stores in patients with CSR and CHF. By increasing oxygen body stores, dampening may be one of the mechanisms responsible for the attenuation of CSR seen with nasal CPAP.

Comparison of positional therapy to CPAP in patients with positional obstructive sleep apnea.

STUDY OBJECTIVES: We hypothesized that positional therapy would be equivalent to continuous positive airway pressure (CPAP) at normalizing the apnea-hypopnea index (AHI) in patients with positional obstructive sleep apnea (OSA). METHODS: Thirty-eight patients (25 men, 49 +/- 12 years of age, body mass index 31 +/- 5 kg/m2) with positional OSA (nonsupine AHI <5 events/h) identified on a baseline polysomnogram were studied. Patients were randomly assigned to a night with a positional device (PD) and a night on CPAP (10 +/- 3 cm H2O). RESULTS: Positional therapy was equivalent to CPAP at normalizing the AHI to less than 5 events per hour (92% and 97%, respectively [p = 0.16]). The AHI decreased from a median of 11 events per hour (interquartile range 9-15, range 6-26) to 2 (1-4, 0-8) and 0 events per hour (0-2, 0-7) with the PD and CPAP, respectively; the difference between treatments was significant (p < 0.001). The percentage of total sleep time in the supine position decreased from 40% (23%-67%, 7%-82%) to 0% (0%-0%, 0%-27%) with the PD (p < 0.001) but was unchanged with CPAP (51% [36%-69%, 0%-100%]). The lowest SaO2 increased with the PD and CPAP therapy, from 85% (83%-89%, 76%-93%) to 89% (86%-9%1, 78%-95%) and 89% (87%-91%, 81%-95%), respectively (p < 0.001). The total sleep time was unchanged with the PD, but decreased with CPAP, from 338 (303-374, 159-449) minutes to 334 (287-366, 194-397) and 319 (266-343, 170-386) minutes, respectively (p = 0.02). Sleep efficiency, spontaneous arousal index, and sleep architecture were unchanged with both therapies. CONCLUSION: Positional therapy is equivalent to CPAP at normalizing the AHI in patients with positional OSA, with similar effects on sleep quality and nocturnal oxygenation.

Effects of oxygen therapy on left ventricular function in patients with Cheyne-Stokes respiration and congestive heart failure.

STUDY OBJECTIVES: Whereas both oxygen therapy and nasal continuous positive airway pressure (CPAP) decrease the apnea-hypopnea index (AHI) in patients with Cheyne-Stokes respiration (CSR) and congestive heart failure (CHF), only nasal CPAP is known to affect the left ventricular ejection fraction (LVEF). We therefore evaluated the effects of 1 month of nocturnal oxygen therapy on LVEF. METHODS: Ten patients (52 +/- 12 years) with CHF (LVEF of 12% +/- 5%) and CSR (AHI 57 +/- 61 events/hour) were studied. Polysomnograms identified CSR and were repeated on oxygen initially (oxygen night 1 [2 L/min]) and after 30 nights (oxygen night 2). LVEF was measured by radionuclide ventriculography. RESULTS: Oxygen therapy decreased the AHI from a baseline of 57 +/- 61 to 9 +/- 11 and 12 +/- 17 events per hour during oxygen nights 1 and 2, respectively (p < .05), with no difference between treatment nights. The lowest oxygen saturation increased during oxygen nights 1 and 2, from a baseline of 87% +/- 7% to 94% +/- 4% and 91% +/- 7%, respectively (p < .05), with no difference between treatment nights. The LVEF did not significantly change from a baseline of 22% +/- 11% to 19% +/- 9% after 1 month of nocturnal oxygen (p = .05). Compared to baseline, there was no change in circulation time during oxygen nights 1 and 2, from 24 +/- 8 seconds to 30 +/- 15 seconds and 23 +/- 6 seconds, respectively (p = .2). Total sleep time, sleep efficiency, and sleep architecture, when compared with baseline, remained unchanged during both oxygen therapy nights. CONCLUSIONS: Although 1 month of nocturnal oxygen therapy decreases the AHI in patients with CSR and CHF, there is no improvement in left ventricular function.