Modulator figure of merit for short reach data links.

The traditional Mach-Zehnder modulator (MZM) figure of merit (FOM) has been defined as (Vπ2)/υ3dBe, and works effectively for LiNbO3 long haul modulators. However, for plasma dispersion based electro-optic modulators, or any modulator that has an inherent relationship between its bandwidth, required drive voltage, and optical insertion loss/gain, this FOM is inappropriate. This is particularly true for short reach links with no optical amplification. In the following, we propose a new modulator FOM (M-FOM) based on device metrics that are essential for short-reach links, such as the peak-to-peak drive voltage, modulator rise-fall time, and relative optical modulation amplitude. Link sensitivity measurements from two MZMs that have different bandwidths and optical losses are compared using our M-FOM to demonstrate its utility. Furthermore, we present a novel application protocol of our M-FOM to provide deeper insight into the relative system impact that modulator performance has on data links with no optical amplification, by taking the ratio of M-FOMs from two modulators driven with the same radio frequency drive power.

Distributed electrode Mach-Zehnder modulator with double-pass phase shifters and integrated inductors.

A novel high-speed Mach-Zehnder modulator (MZM) fully integrated into a 90 nm CMOS process is presented. The MZM features 'double-pass' optical phase shifter segments, and the first use of integrated inductors in a 'velocity-matched' distributed-electrode configuration.

A 25 Gbps silicon microring modulator based on an interleaved junction.

A silicon microring modulator utilizing an interleaved p-n junction phase shifter with a V(π)L of 0.76 V-cm and a minimum off-resonance insertion loss of less than 0.2 dB is demonstrated. The modulator operates at 25 Gbps at a drive voltage of 1.6 V and 2-3 dB excess optical insertion loss, conditions which correspond to a power consumption of 471 fJ/bit. Eye diagrams are characterized at up to 40 Gbps, and transmission is demonstrated across more than 10 km of single-mode fiber with minimal signal degradation.

Multi-array antibody screening in detecting antibodies to mismatched HLA in patients awaiting a second transplant.

Effective identification of HLA specificities to which a prospective transplant recipient has antibodies depends on how effective the most sensitive assay is in detecting these antibodies. To ascertain the assay's efficacy, the results of antibody screening of patients on the waiting list for a second transplant were studied. A commercially available panel of fluoro-coded microbeads coated with multiple and single purified class I or II HLA antigens was used with flow cytometry to detect antibodies in human serum (LABScreen, One Lambda, Canoga Park, Calif, USA). A total of 112 HLA-A, B, and DR mismatches between donors and recipients were present among 34 patients. Antibodies to 56% of the mismatches were detected with 67% of the HLA-A, 38% of the HLA-B, and 63% of the HLA-DR mismatches detected, respectively. Thirty percent of the patients had antibodies to all of the mismatched HLA, 43% had antibodies to some, and 27% did not develop antibodies to any of the mismatched antigens. Among patients who developed antibodies to all of the mismatched HLA, 60% had had a transplant nephrectomy. Only 11% of patients who had no antibodies detected to mismatched HLA had had a transplant nephrectomy and 44% of them were still on immunosuppression. Using the Matchmaker program developed by Duquesnoy, the latter group of patients had a sufficient number of triplet mismatches that could have resulted in an antibody response. All of the undetected antibodies had been identified in other patients in this group. The assay used in this study to detect antibodies is considered the most sensitive one available. Nonetheless, antibodies to slightly less than half of the mismatched HLA antigens were not detected. It appears that the assay system is capable of detecting the antibodies, since in other patients with the same mismatched HLA, antibodies were detected. It is likely that the recipients could develop antibodies since there was a sufficient degree of disparity in the HLA of donors and recipients. Antibodies were more likely to be detected when there had been a transplant nephrectomy and the absence of immunosuppression. There was no way of knowing whether we were missing detecting antibodies or if they were not present. The results of this study have important implications with respect to utilizing "unacceptable antigens" in an allocation system for patients awaiting a second transplant.

Nonoperative therapy for squamous-cell cancer of the esophagus.

Based on the surgical pathology and survival for patients in previous trials using a neoadjuvant program of chemotherapy (5-fluorouracil [5-FU]-cisplatin) and radiation (3,000 cGy) before surgery for squamous-cell cancer (SCC) of the esophagus, a nonoperative pilot trial was designed to test if survival and recurrence would differ from our historical controls if routine esophagectomy was eliminated. Twenty patients were treated. The protocol called for the delivery of 5-FU infusion (1,000 mg/m2/d X 4 d) days 1 to 4 and 29 to 32 with cisplatin (100 mg/m2) day 1 and 29 sandwiched around external beam radiation (3,000 cGy over 3 weeks). Mitomycin C (10 mg/m2) day 57 was administered with bleomycin infusion (20 U/d X 4 d) days 57 to 60 and 78 to 81. A radiation boost of 2,000 cGy was administered 200 cGy/d days 99 to 103 and 106 to 110. Clinical pulmonary toxicity forced withdrawal of bleomycin and mitomycin C in the last four patients treated; two further courses of 5-FU-cisplatin were administered instead. The median measurement of the 20 esophageal lesions by barium swallow was 7 cm. Four patients underwent salvage surgery to prevent life-threatening aspiration pneumonia. The median survival for the 20 patients is 22 months, with a range from 6 to 39+ months. The six patients clinically without cancer are alive 22+ to 39+ months (median, 35+ months). Three patients died manifesting only local (infield) recurrence; five died manifesting only distant recurrence; and five developed local and distant recurrence. While the toxicity of the four drug regimen as administered was prohibitive, the survival and quality of survival is superior to the regimen previously used, which routinely used surgery after preoperative chemotherapy and radiation.

Changes in notification and demographics of deceased donors during the past decade in the state of Michigan, USA.

From 1993 to 2003 there have been significant changes in the number and demographics of deceased donors referred to the organ procurement organization (OPO) in the state of Michigan (USA). It was the aim of this study to document the magnitude of these changes and attempt to explain them. There has been a 26-fold increase in the number of reported in-hospital deaths from 1993 to 2003. Most of these calls (96%) concerned patients who were already dead and thus not suitable for organ donation. There has also been a 72% increase in the number of antemortem calls, but there has been only a 30% increase in the number of organ donors, primarily because the majority of the deceased individuals referred for donation (57% in 2003) do not meet the criteria for brain death. The median age of donors over the past 10 years has increased from 31 to 45. The proportion of African-American donors increased from 9.8% in 1993 to 21.3% in 2003. An increase in the age of donors and the increased frequency of cerebrovascular accidents as the cause of death of donors may be a reflection of changes in criteria for donation. Mandatory reporting of hospital deaths has resulted in an increase in notification to the OPO but has not had a major impact on the number of organ donors. On the other hand, increased donation from African-Americans indicates that public information programs may be contributing to the increased donation from this segment of the population.

The adequacy of informed consent for placement of gastrostomy tubes.

BACKGROUND: Gastrostomy tubes are placed commonly in patients with limited life expectancy. However, it is unclear whether the process of informed consent is adequate in these patients. This study examined the quality of informed consent in hospitalized patients undergoing placement of gastrostomy tubes. METHODS: Retrospective review of the medical records of a cohort of 154 consecutive hospitalized adults undergoing placement of gastrostomy tubes in the context of chronic progressive illness, in the setting of a large community-teaching hospital. RESULTS: The medical record documented a procedure-specific discussion of benefits and burdens of and alternatives to tube feeding in only 1 of 154 patients. Only 12 of 33 definitely or probably competent patients signed the hospital consent form; in the remaining 21, a surrogate decision-maker signed the form. The cumulative 1-year mortality for this cohort was 50%. CONCLUSIONS: The quality of informed consent for placement of gastrostomy tubes was inadequate in a large community-teaching hospital. Indirect evidence from the literature suggests that these results are not unique to this institution. Physicians should become more familiar with the medical and ethical issues relevant to medically administered nutrition near the end of life, and institutions should develop procedures to improve the quality of decision-making for patients considering this intervention.

Cerebrospinal fluid changes in experimental cardiopulmonary bypass using hemodilution with glucose water.

Cardiopulmonary bypass using hemodilution with isotonic glucose water was performed on seven dogs. Intense systemic metabolic acidosis, hyponatremia, hypochloremia, and hyperglycemia were accompanied by only comparatively small changes in the corresponding cerebrospinal fluid values. The data suggested that in the present study, cardiopulmonary bypass was not associated with gross disruptions of the barriers for bicarbonate, sodium, chloride, and glucose between blood and cerebrospinal fluid.

Suppression of human cytotoxic lymphocytes by methylprednisolone. An immunosuppressive mechanism of action of steroids.

In order to gain insight into the immunosuppresive mechanism of action of corticosteroids, an in vitro model of the cellular immune response was used to study the effect of methylprednisolone on human lymphocyte-mediated cytotoxicity. Concentrations from 0.25 to 10 microgram/ml were equally effective in producing 74% suppression lymphocyte-mediated cytotoxicity when the steroid was present during the entire period of in vitro sensitization. A 12.5-fold increase in effector to target cell ratio was required to achieve 30% 51Cr release when cytotoxic lymphocytes were generated in the prescence of methylprednisolone. Lymphocyte-mediated cytotoxicity was suppressed 48% when methylprednisolone was present only during the initial 24 hr of the 7-day in vitro sensitization period. Methylprednisolone also effectively inhibited cytotoxicity when it was incubated with sensitized lymphocytes for 3hr before incubating these cells with target cells. Our observations suggest that two of the major immunosuppressive mechanisms of action methylprednisolone are suppression of the generation of cytotoxic lymphocytes and suppression of specifically sensitized cytotoxic lymphocytes.

Extended treatment with antithymocyte globulin (ATGAM) in renal allograft recipients.

Twenty renal allograft recipients were treated with antithymocyte globulin (ATGAM; ATG) for up to 16 weeks in addition to azathioprine and prednisone, while 20 controls received no ATG. The ATG group showed a lower incidence of first rejection episodes during the first month after transplantation, and also a better functional graft survival rate up to 2 years after transplantation. The results in this early ATG trial were better than those in subsequent trials which used 14-day treatment regimens. Longer treatment deserves another look.

Racial perspectives on kidney transplant donors and recipients.

Prior to undertaking a campaign to increase organ donation, demographic patterns of kidney recipients and donors were examined for our transplant center--the city and state in which it is located (Detroit and Michigan respectively). From 1984 to 1986 there were 964 kidney recipients in Michigan; 28% were black and 69% were white, whereas only 13% of the population in Michigan is black. As has been shown elsewhere in the United States, blacks have more end-stage renal disease than whites and thus require renal transplantation more often. There were 413 kidney donors from Michigan during the same period, 13% were black and 85% were white. In contrast to studies from other parts of the United States, our data show that blacks and whites in Michigan donate kidneys at a similar rate--i.e., 1.5 per 100,000 population. Data such as these should be obtained for areas where campaigns are to be conducted to increase organ donation. This information can be used to educate the public about the needs of the community.

Release, aggregation and lysis of human platelets by antilymphocyte globulin and antiplatelet serum.

Human platelets labeled with 51Cr were used to determine the contribution made by platelet lysis to the platelet release reaction and platelet aggregation induced by rabbit antihuman platelet serum (APS) and equine antihuman thymocyte globulin (ATG). Platelets were tested in both plasma (PRP) and non-plasma containing media. Antibodies directed against platelets, either as APS or ATG, induced significant amounts of platelet release and aggregation, as well as some degree of lysis, in the absence of complement. The presence of complement increased platelet lysis and aggregation, but not the release reaction. Non-immune horse gamma globulin produced different responses depending upon whether platelets were investigated in PRP or non-plasma containing media. Aggregation was seen in the latter but not the former. These differences can be explained by the presence of plasma components which prevent non-specific immune complexes from causing platelet aggregation. Since platelets in vivo are always in a plasma medium, one must be wary of utilizing data from platelet studies in synthetic plasma-free media as the basis of explaining clinical events. These observations demonstrate at least two, and possibly three, different mechanisms whereby ATG could activate platelets causing thrombotic complications and thrombocytopenia, i.e., via 1) specific and, 2) non-specific non-lytic pathways and 3) a lytic pathway.

Randomized clinical trial of preoperative and postoperative adjuvant chemotherapy with cisplatin, vindesine, and bleomycin for carcinoma of the esophagus.

Thirty-nine patients with potentially resectable cancer of the middle or lower esophagus who had not previously been treated were randomly assigned to receive either immediate operation (n = 20) or operation plus preoperative and postoperative therapy with cisplatin, vindesine, and bleomycin (n = 19). Patients were stratified by tumor size and location and by sex, with no significant differences appearing between the two treatment groups. Median follow-up for both groups was 30 months. The preoperative response rate to chemotherapy was 47%. The postoperative complication rate for patients in the operation-only group was 47%; it was 29% for patients receiving chemotherapy. The overall resectability rates were similar for the two groups. Patients responding to chemotherapy preoperatively had significantly prolonged survival (median greater than 20 months) when compared with either nonresponders (median 6.2 months) or patients receiving only operation (median 8.6 months). A highly significant correlation was noted between a weight loss of less than 10% and response to chemotherapy, which suggested that responses occurred in patients with less advanced disease. We conclude that preoperative and postoperative cisplatin, vindesine, and bleomycin chemotherapy has acceptable toxicity and does not increase the incidence of postoperative complications. The natural history of epidermoid carcinoma of the esophagus is altered and overall survival is prolonged for patients responding to preoperative chemotherapy. Potential responding patients can be identified by the degree of preoperative weight loss.

Eradication and palliation of squamous cell carcinoma of the esophagus with chemotherapy, radiotherapy, and surgical therapy.

Between April, 1977, and March, 1981, 86 unselected patients with proved squamous cell carcinoma of the esophagus were treated with a combination of chemotherapy and radiotherapy followed by operation whenever feasible. The preoperative chemotherapeutic agents used initially were 5-fluorouracil, and mitomycin C. After December, 1979, cis-platinum was used instead of mitomycin C. Radiotherapy (3,000 rads) of the tumor was begun at the same time as the chemotherapy. An esophagectomy was performed on suitable candidates 3 to 4 weeks after the chemotherapy and radiotherapy were completed. The mucosal lesion disappeared in 69 of the 86 patients, and dysphagia was relieved at least temporarily in 57 of 62 patients. Recurrent dysphagia resulting from fibrosis at the tumor site caused a secondary stenosis in 11 patients. Excellent palliation was obtained in five patients with bronchoesophageal fistulas who had an initial substernal gastric bypass followed by chemotherapy and radiotherapy. Of the 48 patients who had an esophagectomy, 15 (31%) had no tumor in the resected specimen. Eleven of these 15 patients are still alive with no evidence of disease. All patients with a lesion less than 5.0 cm in length had complete regression of the tumor. We believe that this combination of chemotherapy, radiotherapy, and surgical therapy provides excellent palliation, increases resectability, and has a potential for cure.

The relationship between sleep deprivation and the nocturnal decline of blood pressure.

Blood pressure (BP) has a circadian pattern with a 10% to 15% drop in systolic and diastolic BP comparing nighttime and daytime averages. The mechanism and the "reason" for the decline of nocturnal blood pressure has not been described. If the nocturnal decline is a restorative physiologic process we reasoned that sleep deprivation would increase the nocturnal drop. Thus, we tested the hypothesis that there is a compensatory decline in nocturnal sleep blood pressure after a period of nocturnal sleep deprivation. Twenty-four house staff personnel (normotensive and not taking any BP medications) with a mean age of 29.3 years were recruited for this study (13 men and 11 women). Subjects were randomly assigned to have 24-h BP monitoring after being sleep deprived (on call with 3 +/- 1.3 h of sleep) or after a normal night's sleep (7.3 +/- 0.8 h). There was no significant difference in hours asleep or time to bed or time awake for both 24-h studies. Subjects had similar activities for both monitoring intervals. The percent change in day awake versus night asleep mean values for systolic BP, diastolic BP, and mean arterial pressure for sleep deprived and normal night's sleep intervals were compared using paired t tests. None of these paired parameters were significantly different despite a subjectively "deeper" sleep postcall. In conclusion, sleep deprivation does not appear to result in a compensatory decline in nocturnal blood pressure. Thus, the "reason" for the normal nocturnal decline in blood pressure remains to be explored.

Effect of antithymocyte globulin and other immune reactants on human platelets.

Human platelets suspended in autologous plasma do not respond to nonspecific immune complexes as do platelet suspensions from rabbits and dogs. However, platelets of all three species do undergo aggregation and the release reaction when exposed to antibodies directed against platelets. Antithymocyte globulin (ATG) contains such antibodies, apparently because of antigens common to both thymocytes and platelets. ATG-induced platelet aggregation and release is thus a specific reaction which may be responsible for the thrombocytopenia and thrombotic complications occasionally seen following the administration of ATG. However, if ATG is given properly, its effect on platelets should not constitute a contraindication to the use of this immunosuppressive drug. Since nonspecific immune complexes do not affect human platelets in the presence of plasma, it would appear that platelet aggregates seen in hyperacute and acute rejection result from endothelial damage rather than an effect of immune complexes on platelets.

Perinatal outcome following improvement of abnormal umbilical artery velocimetry.

Umbilical artery velocimetry was investigated to determine whether abnormal flow patterns improved with bed rest and if the prognosis of the pregnancy was different in the improved groups. Abnormal flow waveform was defined as a systolic-diastolic ratio (S/D) above the 95th percentile of established normal values. One hundred twenty-eight women had abnormal waveforms. They were placed on bed rest in the left lateral position and monitored by biophysical profile and growth indices. Sixty-six subjects (51.5%) reverted to normal flow waveforms following bed rest, at a mean (+/- SD) interval of 4.5 +/- 1.5 weeks (range 3-10), and 62 (48.5%) exhibited persistent abnormal flow. None of the improved group exhibited fetal distress or perinatal mortality, whereas in the group with persistent abnormal flow, 15 (24%) experienced fetal distress and 13% experienced perinatal mortality. The diagnosis-to-delivery interval in the improved group was 63 +/- 14 days, versus 26 +/- 21 days in the unimproved group, and the mean gestational age at delivery was 37.3 +/- 2.0 versus 32.8 +/- 3.6 weeks, respectively (P less than .0001). We conclude that a subset of patients with abnormal Doppler velocimetry findings will improve on bed rest and have a better perinatal outcome, whereas persistence of abnormal flow defines a group of patients who are at risk for poor perinatal outcome and who require intensive monitoring and intervention.

Transumbilical placement of the vaginal probe in obese pregnant women.

Transabdominal ultrasonography in obese pregnant women is often unsatisfactory because of the poor transmission of ultrasound through a thickened abdominal wall. We report our experience with the placement of a transvaginal probe in the umbilicus to improve resolution in obese pregnant patients. The technique, which involves filling the umbilicus with ultrasound transmission gel and inserting the transvaginal probe into the umbilicus, was applied in 25 consecutive obese patients who had unsatisfactory fetal imaging by the standard transabdominal approach. The most frequent reason for incomplete fetal survey by the standard transabdominal approach was unsatisfactory imaging of the fetal heart (19 of 25 cases, 76%). The transumbilical approach resulted in improved resolution and satisfactory cardiac examination in 18 of these 19 cases (95%). In two cases, color and pulsed Doppler interrogation of intrafetal vessels become possible. A complete fetal survey was accomplished in 96% of the cases.

Comparison of three sonographic circumference measurement techniques to predict birth weight.

OBJECTIVE: To compare the accuracy of three different sonographic circumference measurement techniques in predicting birth weight in term fetuses, using a standard equation for estimating fetal weight. METHODS: Fifty-three singleton, term fetuses were examined sonographically within 24 hours of scheduled elective cesarean delivery. The biparietal diameter (BPD) and femur length (FL) were measured using standard techniques, and head circumference (HC) and abdominal circumference (AC) were measured using three separate circumference measurement techniques (Two-diameter, ellipse, and trace). With the use of each circumference method, estimated fetal weights were determined for each fetus according to a weight-estimation formula incorporating BPD, HC, AC, and FL. The accuracy of the formula using each circumference measurement technique for predicting actual birth weight was calculated. RESULTS: The mean (+/- standard deviation [SD]) gestational age was 38.1 +/- 0.9 weeks and the mean actual birth weight was 3536 +/- 472 g. The two-diameter and ellipse circumference measurements allowed more accurate birth weight prediction than did the trace method, with mean (+/- SD) percent deviations from the actual birth weight of -0.5 +/- 7.8%, 1.9 +/- 8.0%, and 8.2 +/- 11.6% (P < .05), respectively. The trace method was the least accurate, with a mean birth weight overestimation of 266 g and measurements within 10% of the actual birth weight only 49.1% of the time. The two-diameter and ellipse method yielded predicted birth weights within 10% of actual birth weights in 77.4 and 79.2% of cases, respectively. CONCLUSION: Two-diameter and ellipse circumference measurement techniques are similarly accurate in predicting birth weight and both are significantly better than the trace technique.

A new method using vaginal ultrasound and transfundal pressure to evaluate the asymptomatic incompetent cervix.

OBJECTIVE: To evaluate the ability of ultrasound with transfundal pressure to detect the incompetent cervix in pregnant women at risk for this condition. METHODS: One hundred fifty pregnant women with no prior pregnancy losses were scanned transabdominally, and 31 asymptomatic pregnant women with a prior history of cervical incompetency or risk for this condition were scanned transvaginally. The control patients were scanned once between 16-24 weeks, and the patients at risk were studied 73 times between 8-25 weeks. After evaluating the cervix and its internal os, transfundal pressure was applied. Cervical cerclages were placed for cervical funneling and shortening in response to transfundal pressure or for a grossly incompetent cervix on ultrasound evaluation. RESULTS: Transfundal pressure elicited no changes in the internal cervical os of the 150 control patients, of whom 141 delivered at term, two miscarried at 22 and 23 weeks, and seven delivered prematurely (4.7%). Fourteen of the 31 pregnancies at risk for cervical incompetency revealed opening of the internal os or descent of the fetal membranes with transfundal pressure. Thirteen of these 14 pregnancies were treated with cerclage, with nine (64%) proceeding to term, three (21%) delivering prematurely, and two (14%) aborting. The one patient who did not receive a cerclage also aborted. In six cases, the cervix and its internal os appeared normal but the membranes protruded into the endocervical canal in response to transfundal pressure. CONCLUSION: Application of transfundal pressure during transvaginal ultrasound evaluation of the cervix and its internal os may assist in detecting the asymptomatic incompetent cervix.