Sparse 2-D array design for real time rectilinear volumetric imaging.

Several sparse 2-D arrays for real time rectilinear volumetric imaging were investigated. All arrays consisted of 128x128=16,384 elements with lambda spacing operating at 5 MHz. Because of system limitations, not all of the elements could be used. From each array, 256 elements were used as transmitters, and 256 elements were used as receivers. These arrays were compared by computer simulation using Field II. For each array, beamplots for the on-axis case and an illustrative off-axis case were obtained. For the off-axis case, the effects of receive mode dynamic focusing were studied to maintain the beam perpendicular to the transducer face. Main lobe widths, side lobe heights, clutter floor levels, and pulse-echo sensitivities were quantified for each array. The sparse arrays, including a vernier periodic array, a random array, and a Mills cross array, were compared with a fully sampled array that served as the "gold standard". The Mills cross design showed the best overall performance under the current system constraints.

Changes in endogenous TPO levels during mobilization chemotherapy are predictive of CD34+ megakaryocyte progenitor yield and identify patients at risk of delayed platelet engraftment post-PBPC transplant.

Patients with delayed platelet recovery post-PBPC transplant (PBPCT) are a high-risk group for thrombocytopenic bleeding and platelet transfusion dependence. Total CD34+ cell dosage has been proposed as the most important factor influencing the rate of platelet recovery. To achieve the shortest time to platelet engraftment, a minimum leukapheresis target of 10x10(6) CD34+ cells/kg was established for 30 patients. Of the 29 evaluable patients, 62% had rapid (group I: time to platelets >20x10(9)/l < or =10 days and 50x10(9)/l < or =14 days) platelet recoveries while 38% had delayed (group II: 20x10(9)/l >10 days and 50x10(9)/l >14 days) recoveries. Groups I and II were compared for: (1) pretreatment variables; (2) mobilizing capability of CD34+ cells and subsets including megakaryocyte (Mk) progenitors; (3) infused dose of these cells at transplant; (4) changes in endogenous levels of Mpl ligand (or TPO) during mobilization and myeloablative chemotherapy. Group II patients received significantly more platelet transfusions (6 vs. 2.1, P = 0.002) post-PBPCT, had a higher proportion of patients with a prior history of BM disease (64% vs. 6%, P = 0.001), and showed a reduced ability to mobilize differentiated (CD34+/38+, CD34+/DR+) and Mk progenitors (CD34+/42a+, CD34+/61+). Only the number of Mk progenitors reinfused at transplant was significantly different between the groups (group II vs. group I: CD34+/42a+ = 1.02 vs. 2.56x10(6)/kg, P = 0.013; CD34+/61+ = 1.12 vs. 2.70x10(6)/kg, P = 0.015). The ability to mobilize Mk progenitors correlated with percentage changes in endogenous levels of TPO from baseline to platelet nadir during mobilization chemotherapy (CD34+/42a+: r = 0.684, P = 0.007; CD34+/61+: r = 0.684, P = 0.007), with group II patients experiencing lower percentage changes. An inverse trend but no correlation was observed between serial TPO levels and platelet counts. TPO levels remained elevated in group II patients throughout a prolonged period of thrombocytopenia (median days to 50x10(9)/l = 25 vs. 11 for group I), indicating that delayed engraftment was not due to a deficiency of TPO but to a lack of Mk progenitor target cells. Our results show that the number of reinfused Mk progenitors is a better predictor of platelet engraftment than total CD34+ cell dosage. Small changes in endogenous TPO levels during mobilization predict for low Mk progenitor yields.

Indinavir crystalluria: identification of patients at increased risk of developing nephrotoxicity.

OBJECTIVE: To determine whether the protease inhibitor indinavir sulfate, which is extremely insoluble at physiologic pH levels and which is known to be associated with nephrolithiasis, is associated with crystalluria at a usual therapeutic dose. METHODS: Freshly voided urine from 27 male human immunodeficiency virus patients being treated with indinavir at a dose of 800 mg, tid, in an outpatient setting and from 20 healthy subjects undergoing routine physical examination was subjected to dipstick urinalysis and microscopic examination of urinary sediments. RESULTS: Three (11%) of 27 patients treated with indinavir developed highly characteristic crystalluria during the course of therapy. No such crystals were observed in the urine of the 20 healthy subjects. CONCLUSION: Indinavir crystalluria was identified in asymptomatic patients treated with usual therapeutic doses of the drug. Screening urines of patients taking indinavir may be useful in identifying patients at risk for developing nephrotoxicity.

Exogenous Neisseria meningitidis endophthalmitis.

PURPOSE: To report a case of Neisseria meningitidis endophthalmitis in association with a leaking filtering bleb and to consider antibiotic prophylaxis of those people with whom the patient had contact. METHOD: We treated an 81-year-old man who had a chronic, leaking filtering bleb and who developed exogenous N meningitidis endophthalmitis. RESULT: N meningitidis endophthalmitis was controlled with antibiotic therapy. Antibiotic prophylaxis for those with whom the patient had contact was not recommended. CONCLUSION: In this case, the N meningitidis strain was not considered invasive because the bacteria apparently entered the eye through a leaky filtering bleb and not through the bloodstream. Recovery of noninvasive N meningitidis does not require prophylaxis for patient contacts. In cases of endogenous or idiopathic N meningitidis endophthalmitis, antibiotic prophylaxis of close patient contacts may be warranted.

Nosocomial and community-acquired Staphylococcus aureus bacteremias from 1980 to 1993: impact of intravascular devices and methicillin resistance.

The rate of nosocomial bacteremia due to Staphylococcus aureus has increased over the past decade, but trends in community-acquired S. aureus bacteremia are less certain. This hospital-based observational study compares nosocomial and community-acquired S. aureus bacteremias during 1980-1983 and 1990-1993. The rate of nosocomial S. aureus bacteremia increased from 0.75 to 2.80 cases per 1,000 discharges, while the rate of community-acquired S. aureus bacteremia increased from 0.84 to 2.43 cases per 1,000 discharges. The number of nosocomial device-related bacteremias increased eightfold; 56% of S. aureus bacteremias were associated with devices during 1990-1993. Intravascular devices were associated with no community-acquired S. aureus bacteremias during 1980-1983 but with 22% during 1990-1993. Methicillin-resistant S. aureus (MRSA) seldom caused bacteremia during 1980-1983. From 1990 to 1993, MRSA caused 32% and 18.5% of nosocomial and community-acquired S. aureus bacteremias, respectively. The rates of both community-acquired and nosocomial S. aureus bacteremias have increased significantly since 1980. In addition to their role in nosocomial infections, MRSA and intravascular device-related S. aureus bacteremias are emerging problems in the nonhospital setting.

Osteomyelitis of the sternum caused by Apophysomyces elegans.

Apophysomyces elegans, a member of the family Mucoraceae, was found to infect the chest wall and sternum of an immunocompetent man following minor trauma. As in previous cases, amphotericin B therapy alone was inadequate. Extensive surgical debridement was required in order to eradicate the infection.

Culture isolation of Acanthamoeba species and leptomyxid amebas from patients with amebic meningoencephalitis, including two patients with AIDS.

Acanthamoeba species and leptomyxid organisms are free-living amebas that cause meningoencephalitis, primarily in immunocompromised patients. We report the isolation and culture of Acanthamoeba species and leptomyxid amebas from four patients with fatal amebic meningoencephalitis. Acanthamoeba species were cultured from brain abscess specimens from three immunocompromised patients (including two patients with AIDS). In the case of the fourth patient, who had no identifiable immunodeficiency, leptomyxid amebas were cultured from a specimen from a subcutaneous nodule and were identified in amebic granulomas in brain tissue by the indirect immunofluorescence test. Persons with advanced infection due to the human immunodeficiency virus may be at increased risk for amebic meningoencephalitis, but the diagnosis should be considered in the differential diagnosis of any immunocompromised patient with cerebral abscesses.

Suppurative cervical lymphadenitis after Yersinia enterocolitica bacteremia.

Yersinia enterocolitica is increasingly recognized as a pathogen causing diverse complications. We have reported the case of a man with fever, abdominal tenderness, and Y enterocolitica bacteremia. After antibiotic therapy, his condition improved initially, but later, suppurative cervical lymphadenitis developed. This suggests that the hematogenous spread of Y enterocolitica to a distal lymphatic focus of infection is a possible complication of Y enterocolitica bacteremia.

Predictors of outcome in AIDS patients receiving zidovudine.

Fifty-eight AIDS patients who previously had Pneumocystis carinii pneumonia (PCP) were enrolled in an open trial of zidovudine therapy. We analyzed baseline clinical and laboratory parameters to identify predictors of outcome. Fifty-eight patients were followed for a mean of 26.5 weeks. There were 17 deaths; the probability of survival at 24 weeks was 0.81. Forty-one participants had unsuccessful outcomes, which included new opportunistic infections (24), progressive neurologic deterioration (2), and drug toxicity, excluding anemia, necessitating discontinuation of zidovudine (15). Only 24 subjects (41%) were receiving zidovudine at the end of the study period including 17 who had neither opportunistic infection nor toxicity. Low baseline hemoglobin level (p less than 0.001) and poor performance status as measured by the Karnofsky scale (p less than 0.01) independently predicted unsuccessful outcome and early death. Low hemoglobin (p = 0.001), low platelet count (p = 0.016), and increased time since PCP (p = 0.008) predicted development of drug toxicity. Neither CD4 lymphocyte count nor p24 antigenemia correlated with outcome.

The nature of insulin secretory defect in aging rats.

We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface membrane. Section vesicle lysis was studied by measuring insulin release into the incubation media. Submaximal and maximal glucose-induced insulin secretion was significantly greater in islets isolated from younger rats (P less than 0.01). SRIF receptor recruitment was stimulated by glucose in both younger and older Fischer 344 rats. However, an increase in SRIF receptor recruitment was reduced in islets isolated from older animals (from 2.14 +/- 0.4 to 4.6 +/- 0.4 fmol/10 islets) (P less than 0.01) as compared with islets from younger animals (from 2.6 +/- 0.2 to 6.2 +/- 0.4 fmol/10 islets). When secretion vesicle lysis was inhibited by the presence of sodium isethionate in the incubation media, glucose (300 mg/dl) failed to stimulate secretion vesicle margination to the plasma membrane. In contrast, glyburide (0.6 micrograms/ml) continued to stimulate directly secretion vesicle margination in islets from aged animals (from 2.1 +/- 0.3 to 6.0 +/- 0.3 fmol/10 islets). We conclude that glucose-induced margination of secretion vesicles at the plasma membrane is impaired by the aging process. This impairment results in lower submaximal and maximal insulin secretory response to glucose. The fact that glyburide is capable of stimulating secretion vesicle margination suggests that glucose signal recognition and/or stimulus-secretion coupling may be the locus of impairment in the process of insulin secretion in older animals.

Control of secretion vesicle margination and lysis by glucose, IBMX, and glyburide.

We have attempted to define the effect of glucose, glyburide, and isobutylmethylxanthine (IBMX) upon secretion vesicle margination to the plasma membrane and granule lysis. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors. Secretion vesicle lysis was studied by measuring insulin release into the incubation media. Our observations suggest that glucose directly affects both secretion vesicle margination and lysis. Both events are rapidly influenced by this secretagogue (within 10 min of incubation). Trifluoperazine (TFP) and removal of Ca2+ from the incubation media significantly reduced glucose-induced margination of secretion vesicles and their lysis (P less than 0.001). IBMX primarily influences the lysis of secretion vesicles and not their margination. IBMX caused a rapid increase in insulin secretion within 10 min without recruitment of SRIF receptors. Neither TFP nor the absence of extracellular Ca2+ affected IBMX-induced insulin release. Late enhancement in margination of secretion vesicles (30 min of incubation with IBMX) is probably related to the initial event of secretion vesicle lysis and is independent of extracellular calcium. Glyburide exerts its action in a manner similar to glucose, affecting both the lysis of secretion vesicles and their margination. However, the action of glyburide is independent of extracellular calcium and partially dependent upon calmodulin.

Calmodulin and cyclic AMP. Possible different sites of action of these two regulatory agents in exocytotic hormone release.

It may now be possible to identify certain intracellular events that impact specifically on secretion-granule fusion to the plasma membrane or on granule lysis. Secretion vesicles in isolated rat islets appear to translocate somatostatin (SRIF) receptors from the Golgi apparatus to the plasma membrane. We have proposed that secretion granule fusion to the plasma membrane can be determined by measuring recruitment of SRIF receptors to the surface membrane. Granule lysis can be assessed by measuring insulin release. To activate cyclic AMP (cAMP)-dependent pathways, we employed isobutylmethylxanthine (IBMX, 400 microM), glucagon (10 microM), and forskolin (20 microM), a diterpene activator of adenylate cyclase. These agents evoked rapid release of insulin (from 0.41 +/- 0.02 to 1.88 +/- 0.02; 0.41 +/- 0.02 to 1.93 +/- 0.08; and 0.41 +/- 0.02 to 1.66 +/- 0.03 microU/islet/min, respectively, P less than 0.001). There was no concomitant recruitment of SRIF receptors. Somatostatin (10 micrograms/ml), which inhibits cAMP-stimulated protein phosphorylation, suppresses insulin release evoked by IBMX, glucagon, or forskolin (inhibition: 80, 75, or 82%, respectively). In contrast, trifluoperazine (10 microM), an inhibitor of calmodulin, did not suppress insulin release induced through cAMP-dependent pathways. Trifluoperazine suppresses glucose-induced insulin release and the recruitment of SRIF receptors to the surface membrane, suggesting the possible role of calmodulin in promoting secretion-granule fusion with the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)