Four-channel polarization-insensitive optically transparent wavelength converter

Multichannel wavelength converters may be important components in the cross-connects in future wavelength-division multiplexed (WDM) transport networks. We demonstrate a multichannel, polarization-insensitive, optically transparent wavelength converter, based on four-wave mixing in two semiconductor optical amplifiers in a polarization-diversity arrangement. Bit-error-rate (BER) measurements with four input 2.5-Gb/s WDM channels, spaced by 2 nm, show penalties for wavelength conversion less than 2.6 dB at 10/sup -9/ BER. Changes in the state of polarization of the input signals cause the output power to change by less than 1.2 dB, and the corresponding power penalties change by less than 0.9 dB.     

Iodo-2'-deoxyuridine (IUdR) and 125IUdR loaded biodegradable microspheres for controlled delivery to the brain

The aim of this work was to develop sustained local release systems for radioiodinated iodo-2'-deoxyuridine (125IUdR) from biodegradable polymeric microspheres to facilitate the controlled delivery of 125IUdR to brain tumours. The selective uptake of IUdR into the cell nucleus results in cell disruption over the short range of the low energy Auger electrons. The biodegradable microspheres can be precisely implanted in the brain by stereotactic techniques and the IUdR within the microspheres is protected from degradation and thus a sustained source of radiolabelled IUdR is available in the vicinity of the residual tumour cells. Poly(lactic-co-glycolic acid), PLGA (85:15), microspheres containing cold IUdR and the Auger-electron emitter 125I, as 125IUdR were prepared using the O/W, O/O and W/O/W emulsion-solvent evaporation methods. The W/O/W emulsion method was most effective in achieving good drug loading with the use of bovine plasma in the internal water phase. Also effective in improving the drug loading was the use of 20% acetone in the dichloromethane and the presence of Span 40 in the organic phase. Electrolytes (NaCl and IUdR) in the external aqueous phase also improved drug loading. After an initial rapid release from the microspheres, a sustained release was observed over 15 days for the 'cold' IUdR. The sustained release portions of the release curves showed Higuchi (t1/2), diffusion controlled release kinetics. The radiolabelled IUdR microspheres showed a burst release effect of 30-40% followed by a sustained release over 35 days.     

Infections in patients with cystic fibrosis following lung transplantation

BACKGROUND: There is controversy over whether colonization with drug-resistant organisms is a contraindication to lung transplantation. METHODS: We undertook a retrospective review of the results of lung transplantation for patients with cystic fibrosis (CF) at Duke University Medical Center. RESULTS: As of May 1996, 21 patients with CF underwent bilateral lung transplantation. The first patient died within 24 h of transplantation from sepsis due to Stenotrophomonas maltophilia. Of the remaining 20 patients, 17 (85%) are alive and in stable condition. The three deaths were related primarily to bronchiolitis obliterans at 4 and 18 months in two patients and to cytomegalovirus pneumonitis at 5 months in the other patient. The 17 surviving patients have been followed up for a mean of 13 months (range, 0.5 to 34 months). Most of them were colonized and infected with multidrug-resistant organisms before transplantation. Following transplantation, 11 patients had complications from infections. One patient had bacteremia due to a panresistant Burkholderia cepacia and was treated successfully. Two patients had bacteremia and wound infection due to Burkholderia gladioli, previously thought to be pathogenic only in plants. Both patients were treated successfully. Of the six patients with Aspergillus fumigatus isolated from cultures before transplantation, only one had invasive disease following transplantation and responded to treatment. CONCLUSION: The organisms present before transplantation were not the primary cause of mortality in our patient population. Our findings suggest that lung transplantation should be considered in CF patients infected with multidrug-resistant organisms.     

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia

PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC.     

Role of hepatic resection in surgery for bilateral intrahepatic stones

The effect of phenylephrine-induced reflex parasympathetic stimulation on QT interval and its dispersion was studied in 16 healthy subjects with a history of paroxysmal supraventricular tachycardia, both during sinus rhythm and during atrial pacing. Results demonstrate that rapid reflex parasympathetic stimulation does not influence QT interval duration or QT dispersion, and also emphasize the inappropriateness of Bazett's formula, the need for comparison of QT intervals during identical heart rates, and the importance of analyzing all 12 leads of a standard electrocardiogram when assessing the effects of various interventions on the QT interval.     

The lack of long-term detrimental effects on liver allografts caused by donor-specific anti-HLA antibodies

Recent reports indicate a higher incidence of both acute and chronic liver allograft rejection when, at the time of transplantation, the recipients serum contains donor-specific anti-HLA antibodies. From 9/89 to 5/91, 133 liver allografts were performed at our institution. Thirteen liver recipients had donor-specific IgG anti-HLA antibodies (complement-fixing) at the time of transplantation. In eleven patients, antibodies reacted to donor class I antigens while in 1 patient the donor-specific antibody had class II reactivity. Twelve patients have been followed for a minimum of 12 months (median 18 months, range 28-12 months). No hyperacute rejection was seen in any of the cases and four patients had acute rejections. Thus far only one of the twelve patients has biopsy evidence suggestive of chronic liver injury. The remaining have normal liver enzymes and bilirubin. Three of these twelve patients died (one from a myocardial infarction and the others from sepsis) accounting for a one-year graft survival of 75%. There was no significant statistical difference in the one-year graft survival in those recipients without donor-specific antibodies (i.e., 80.5%). In eight of the twelve patients, pretransplant preformed antibody level (PRA) was > 50%. In six of the thirteen patients donor-specific antibody was present at dilutions greater than 1:64. As previously reported, the donor-specific antibody disappeared from the serum posttransplant within hours and did not reappear. In vitro studies demonstrated no factor in portal or hepatic artery blood that could inhibit rabbit complement mediated lysis of anti-HLA antibodies. We conclude that it is not a contraindication to do liver transplants in the presence of donor-specific anti-HLA antibodies.     

Delay discounting of real and hypothetical rewards.

The degree to which real and hypothetical rewards were discounted across delays ranging from 6 hr to 1 year was explored in a within-subjects design. An adjusting-amounts procedure was used to estimate the subjective value of real and hypothetical rewards at each delay. A hyperbolic discounting function provided a significantly better fit to individual participants' preferences than did an exponential function. No significant effect of reward type on degree of hyperbolic discounting or area under the discounting curves was detected. These findings offer some support for the validity of using hypothetical rewards to estimate discounting rates in substance-abusing and other populations, but caution is suggested because this support is gleaned from a failure to detect an effect of reward type. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcoholism: independent predictor of survival in patients with head and neck cancer

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.     

Endothelin-1 concentrations and optimisation of arterial oxygenation and venous admixture by selective pulmonary artery infusion of prostaglandin E1 during thoracotomy

PURPOSE: To demonstrate a superselective intraarterial chemotherapy as a therapeutic alternative in the treatment of previously treated recurrent lymph node metastases in breast cancer. METHODS: 14 patients with recurrent lymph node metastases in cases of breast cancer were presented to be treated by intraarterial chemotherapy of 25 mg mitoxantrone/m2 over a period of 24 hours. In two patients with superclavicular lymph node involvement an intraarterial therapy could not be carried out because of a vascular connection to the anterior spinal artery. Involved lymph stations could be reached in superselective technique by side branches of the subclavian artery. Heparin coverage was given intravenously. Every patient had had surgery, radiation, systemic chemo- and hormonal therapy before and was now graded as inoperable. Therapy indication was given by local tumour-induced symptoms. RESULTS: In the 12 treated cases complete remission was seen in three, partial remission in 4, a steady state in two and a progressive disease in three. There were no complications or severe side effects. CONCLUSION: Intraarterial chemotherapy is an effective and well tolerated treatment in recurrent lymph node metastases in cases of breast cancer even if conventional therapies can no longer be used.