Improved resolution and signal-to-noise ratio in MRI via enhanced signal digitization.

The high frequency k-space data in magnetic resonance imaging is often poorly reproduced due to the finite dynamic range of an analog-to-digital converter. The magnitude of this digitization error can equal and even exceed the magnitude of the thermal noise. Under such conditions, attempts to increase image signal-to-noise ratio via signal averaging meet with diminishing success. Because the relative size of the digitization error increases at higher spatial frequencies, a reduction in image resolution is incurred as well. By adjusting the level of the analog signal sampled by the analog-to-digital converter during the course of an imaging experiment, the magnitude of the digitization artifact can be greatly reduced. The results of simulations and imaging experiments are presented which demonstrate that this strategy improves both the signal-to-noise ratio and resolution of magnetic resonance images.

Fast imaging of phosphocreatine using a RARE pulse sequence.

A technique is described for acquiring phosphocreatine (PCr) images of skeletal muscle using a rapid acquisition with relaxation enhancement (RARE) pulse sequence. All of the phosphorus metabolites other than PCr are forced to dephase within the first few echoes, whereas the Carr-Purcell Meiboom-Gill (CPMG) pulse sequence maintains a high PCr signal long enough to acquire 64 echoes in a single shot. Axial PCr images of a human forearm with a signal-to-noise ratio of 9 were acquired in 2 min. The effect of the refocusing pulse section profile on the ratio of desired to undesired metabolite signal is demonstrated.

Bilateral imaging using separate interleaved 3D volumes and dynamically switched multiple receive coil arrays.

Multiple receive coil arrays are often designed for unilateral imaging of anatomy having bilateral symmetry. A technique is described for extending the utility of such arrays to simultaneously image both bilaterally symmetric anatomical features. A separate, complete multiple receive coil array is placed at each location. Two separate, noncontiguous 3D volumes are then acquired, one at each location, in an interleaved fashion. High-impedance blocking networks are alternately activated and deactivated to minimize coupling between the arrays. It is demonstrated that there is no degradation in image quality when compared to a unilateral exam. A general method for analyzing the interactions between separate multiple coil arrays is presented.

Fine-needle aspiration biopsy in the diagnosis of parotid gland lesions: evaluation of 438 biopsies.

The usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis and treatment of salivary gland lesions is still controversial. The 438 FNABs taken at the Turku University Central Hospital between 1984-1991 were reviewed. Of these FNABs, 218 had been confirmed histologically. Within this subset, 136 FNABs were taken from benign neoplasms, and of these, 103 were correct (sensitivity 76%, specificity 83%). Only 26 of the 47 FNABs from malignant lesions were cytologically considered to be malignant (sensitivity 55%) and 11 samples raised a false suspicion of malignancy (specificity 92%). Out of 35 FNABs from non-neoplastic lesions, 27 were correct (sensitivity 77%, specificity 80%). There were 175 patients (217 FNABs), who had not been operated on: the follow-up of these patients showed that false malignant and false benign findings were rare. FNAB was safe and no serious complications occurred. However, there was a delay in the treatment of six patients probably because of the physicians' limited understanding of the diagnostic role of FNAB. FNAB offers valuable information about the type of parotid lesion, but the clinician must know how to interpret the cytologic statement, and the decision to use operative and other treatment should not be based solely on the result of FNAB. Diagn Cytopathol 1996; 15:185-190.

Hantavirus pulmonary syndrome in Florida: association with the newly identified Black Creek Canal virus.

Hantavirus pulmonary syndrome (HPS) is a recently recognized viral zoonosis. The first recognized cases were caused by a newly described hantavirus. Sin Nombre virus (previously known as Muerto Canyon virus), isolated from Peromyscus maniculatus (deer mouse). We describe a 33-year-old Floridian man who resided outside the ecologic range of P maniculatus but was found to have serologic evidence of a hantavirus infection during evaluation of azotemia associated with adult respiratory distress syndrome. Small mammal trapping conducted around this patient's residence demonstrated the presence of antihantaviral antibodies in 13% of Sigmodon hispidus [cotton rat). Serologic testing using antigen derived from the Black Creek Canal hantavirus subsequently isolated from this rodent established that this patient was acutely infected with this new pathogenic American hantavirus. HPS is not confined to the geographical distribution of P maniculatus and should be suspected in individuals with febrile respiratory syndromes, perhaps associated with azotemia, throughout the continental United States.

Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group.

OBJECTIVE: To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhIL-1ra) in the treatment of sepsis syndrome. STUDY DESIGN: Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. POPULATION: A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. OUTCOME MEASURE: Twenty-eight-day all-cause mortality. RESULTS: There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n = 893; generalized Wilcoxon statistic, P = .22) or among patients with shock at study entry (n = 713; generalized Wilcoxon statistic, P = .23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n = 563; linear dose-response, P = .009). Retrospective analysis demonstrated an increase in survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n = 580; linear dose-response, P = .005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n = 411; linear dose-response, P = .002). CONCLUSIONS: There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater.

A controlled clinical trial of E5 murine monoclonal IgM antibody to endotoxin in the treatment of gram-negative sepsis. The XOMA Sepsis Study Group.

OBJECTIVE: To assess the efficacy of adjunctive monoclonal antibody antiendotoxin immunotherapy in patients with gram-negative sepsis. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Thirty-three university-affiliated centers, including Veterans Affairs, community, and municipal hospitals. PATIENTS: Hospitalized adults with signs of gram-negative infection and a systemic septic response. INTERVENTION: Patients were assigned to receive either 2 mg/kg of a murine monoclonal antibody directed against gram-negative endotoxin (E5) or placebo. A second infusion was administered 24 hours later. MAIN OUTCOME MEASURES: Mortality over the 30-day study period, resolution of organ failures, and safety. RESULTS: Four hundred eighty-six patients were enrolled. Three hundred sixteen had confirmed gram-negative sepsis (54% bacteremic, 46% nonbacteremic). The survival difference was not statistically significant for all patients. Among patients with gram-negative sepsis who were not in shock at study entry (n = 137), E5 treatment resulted in significantly greater survival (relative risk, 2.3; P = .01). Resolution of individual organ failures was more frequent among these patients, occurring in 19 (54%) of 35 patients in the E5 group vs eight (30%) of 27 in the placebo group (P = .05). Four reversible allergic reactions occurred among 247 patients (1.6%) receiving E5. No other toxicity was identified. CONCLUSIONS: Treatment with E5 antiendotoxin antibody appears safe. It reduces mortality and enhances the resolution of organ failure among patients with gram-negative sepsis who are not in shock when treated.

Isolated erythroid hypoplasia and renal insufficiency induced by long-term griseofulvin therapy.

We describe a patient with hematuria, pyuria, eosinophiluria, decreased renal function, and severe anemia that developed while she was receiving chronic therapy with griseofulvin for onychomycosis. We offer evidence that griseofulvin can cause an isolated erythroid hypoplasia and possibly an allergic interstitial nephritis. This is the first documented case of the above entities induced by the agent. We would recommend, based on our report, that otherwise healthy patients, when maintained on the drug for extended periods of time, have periodic determinations of renal function and hematologic status. As drug-induced erythroid hypoplasia typically occurs after a relatively long period of dosing, it may be prudent in certain individuals to monitor the CBC at approximately bimonthly intervals after initiation of therapy. Recommendations regarding monitoring of renal function are more difficult, as acute allergic interstitial nephritis can occur after either short- or long-term exposure to certain drugs.

Successful treatment of gram-negative bacillary meningitis with imipenem/cilastatin.

A patient with meningitis caused by a strain of Actinetobacter anitratus that was resistant to all commercially available antibiotics was treated with imipenem/cilastatin administered intravenously in a dose of 1 gm of imipenem every six hours. The minimal inhibitory concentration of imipenem against the isolate was less than or equal to 0.04 micrograms/ml. The patient tolerated the drug well and was cured after 12 days of therapy.

Efficacy of imipenem/cilastatin in endocarditis.

Imipenem, a potent new beta-lactam antibiotic, which is bactericidal against most pathogenic bacteria, and cilastatin, a dehydropeptidase inhibitor combined with imipenem to prevent the metabolism of imipenem in the kidney, were evaluated in the treatment of bacterial endocarditis. Seventeen patients, including 14 who used intravenous drugs, were treated with imipenem/cilastatin in a dose of 500 mg each infused over 30 minutes every six hours. The mean duration of treatment was 29 days with a range of 21 to 56 days. Causative bacteria were Staphylococcus aureus in 10 patients, S. aureus plus group B Streptococcus in one, viridans group Streptococcus in two, Neisseria subflava, Eikenella corrodens, and group G Streptococcus in one patient, and Staphylococcus epidermidis, Hemophilus aphrophilus, and Enterobacter aerogenes in one patient each. The minimal bactericidal concentration of imipenem against 16 of 18 isolates tested was 0.04 micrograms/ml, 1 microgram/ml against H. aphrophilus, and 0.4 micrograms/ml against E. aerogenes. The site of infection was the right side of the heart in 11 patients, the left side in five, and both sides in one. The mean number of days to defervescence was 9.7. All patients were cured, and none required cardiac surgery. Adverse effects were few and interrupted treatment occurred in only one patient who had acute dyspnea during an infusion on Day 26 of therapy. Imipenem/cilastatin appears to be a relatively safe and highly effective treatment of staphylococcal endocarditis in intravenous drug users; too few patients with endocarditis caused by other bacteria were treated to allow a firm statement about efficacy in non-staphylococcal endocarditis.

Penetration of aztreonam into human cerebrospinal fluid in the presence of meningeal inflammation.

Cerebrospinal fluid of aztreonam were measured in 11 patients with meningeal inflammation. Two to eight hours after a single 2 gm intravenous dose, CSF aztreonam levels ranged from 0.76 to 16.6 mg/l. The mean CSF concentration in four patients with viral meningitis was 1.28 mg/l, which was lower than the mean concentration of 7.2 mg/l in the five with bacterial, cryptococcal or carcinomatous meningitis. Two patients with infected subdural drains were also sampled serially and had CSF levels greater than 1 mg/l between 1 and 8 h post dose. Penetration of aztreonam into the CSF in the presence of meningeal inflammation appears adequate to warrant therapeutic trials in patients infected with susceptible organisms.

Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers.

Twice-daily intramuscular ceforanide therapy of Staphylococcus aureus endocarditis in parenteral drug abusers was compared in a randomized prospective trial with intravenous cephapirin therapy. Dosage regimens were ceforanide, 1 g every 12 h, and cephapirin, 2 g every 4 h. Mean minimal inhibitory and bactericidal concentrations of ceforanide for S. aureus treated with ceforanide were 0.78 and 1.56 microgram/ml compared to cephapirin for patient isolates of 0.08 and 0.14 microgram/ml, respectively. Serum killing levels with ceforanide were 1:5.7 and 1:1.5 at peak and trough levels, compared to 1:134 (peak) and 1:4.2 (trough) with cephapirin. Despite this apparent in vitro advantage of cephapirin, patients treated with ceforanide did as well as those with cephapirin. Of 16 ceforanide-treated patients, all responded initially to therapy, and 15 were cured with 28 days of therapy. One patient relapsed at the end of therapy. Of 16 cephapirin-treated patients, 1 was a clinical and microbiological failure, and 3 other relapsed at the end of therapy. In addition, one ceforanide-treated patient and two cephapirin-treated patients developed central nervous system abscesses. These were cured with drainage and continuation of antibiotic therapy. Ceforanide was well tolerated by the intramuscular route. Cost analysis suggests that therapy with intramuscular ceforanide would result in an approximate 70% decrease in drug therapy cost when compared to intravenous cephapirin. Ceforanide appears to be a safe, efficacious, convenient, and relatively inexpensive drug for treating staphylococcal endocarditis in parenteral drug abusers.

Toxoplasma encephalitis in recent Haitian entrants.

We evaluated clinical features of five cases of Toxoplasma encephalitis (TE) occurring in recent Haitian entrants into the United States. None of the patients had any underlying malignancy or known immunosuppressive therapy. Histopathologic findings of TE at autopsy were confirmed by peroxidase-antiperoxidase method. Four patients had an antecedent episode of disseminated tuberculosis and all five were receiving antituberculous therapy when neurologic manifestations of lethargy, seizures, and motor weakness first developed. These symptoms progressed into coma and death within 15 days. Peripheral lymphocytopenia was noted in all patients; three were anergic. Parenchymal lesions were identified by CT brain scans and total proteins were elevated in spinal fluid in all cases. TE appears to be a manifestation of the acquired immune deficiency syndrome in Haitians; it should be suspected in those with a febrile illness and multiple focal lesions of the central nervous system.

Clinical evaluation of piperacillin with observations on penetrability into cerebrospinal fluid.

Piperacillin, a new semisynthetic penicillin, was evaluated for efficacy and safety in 26 patients, most of whom had pneumonia. Included were four patients with gram-negative meningitis in whom the penetration of piperacillin into cerebrospinal fluid was determined. Cure was achieved in 11 of 17 patients with pneumonia; another 4 were improved. One relapse and one failure occurred among nine patients with gram-negative pneumonia. Cure or improvement occurred in seven of nine patients with gram-negative infection in various extrapulmonary sites. Piperacillin given by continuous infusion in a dosage ranging from 324 to 436 mg/kg of body weight per day to four patients with meningitis resulted in a mean cerebrospinal fluid level of 23 micrograms/ml at 24 h; the mean penetration of piperacillin into the cerebrospinal fluid was 32% at this interval. Levels of piperacillin in cerebrospinal fluid collected later during the course of therapy were also adequate. Adverse effects were noted in six patients, but only one episode of granulocytopenia was serious. Emergence of resistance to piperacillin did not occur, and only one superinfection was noted. Piperacillin appeared to be efficacious in the treatment of pneumonia. It penetrated well into the cerebrospinal fluid of patients with meningitis and may be useful for treatment of selected gram-negative infections in extrapulmonary sites.

Multifocal sporotrichosis presenting with lobar pulmonary consolidation.

A case of multifocal systemic sporotrichosis presenting with lobar pneumonia caused by Sporothrix schenkii is described. While five cases of pulmonary involvement in multifocal sporotrichosis have been previously reported, all had nodular or cavitary apical lesions. Similarly, unifocal pulmonary sporotrichosis usually presents with apical cavitary disease. The presence of skin nodules led to a culture diagnosis of sporotrichosis of the skin and prompted further diagnostic studies to elucidate the etiology of the pneumonia.

A fatal case of Legionnaire's disease following a total laryngectomy.

Legionnaire's disease (LD) has been responsible for the death of many patients in several outbreaks in the United States and abroad. The Legionnaire's bacterium is still unclassified. Deoxyribonucleic acid studies of its genes have not yet found a near relative. A case of a 63-year-old man who had a total larynegectomy for cancer of the larynx is reported. He had an extensive postoperative pneumonia, secondary to LD. The diagnosis was made while the patient was alive, but he died on the 35th hospital day in spite of erythromycin treatment.

Single or combination therapy of staphylococcal endocarditis in intravenous drug abusers.

Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.

Staphylococcal endocarditis in addicts.

We retrospectively reviewed 55 episodes that fulfilled criteria for Staphylococcus aureus endocarditis in 50 drug addicts. The most common presenting symptoms were fever(90%), chest pain(58%), and cough(43%). All patients had evidence of right-sided heart involvement, and a murmur of tricuspid insufficiency was noted in 42%. Evidence of left-sided heart involvement was present in only 5%. The most helpful laboratory aid in facilitating an early clinical diagnosis of endocarditis was the chest x-ray film. Roentgenographic evidence of septic pulmonary emboli was present in 67% of initial chest films and eventually in 87% of all cases. All but five patients completed at least four weeks of intravenous antibiotic therapy. No patients required cardiac surgery and there were no deaths. The apparent predilection of S aureus for the right side of the heart and infrequent left-sided involvement may explain why addicts with endocarditis have a favorable response to antibiotic therapy.