High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial.

Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FiO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FiO2.300mmHg for at least 24 hours, the proportion of participants with a PaO2/FiO2.300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FiO2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FiO2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.

Inhaled high dose nitric oxide is a safe and effective respiratory treatment in spontaneous breathing hospitalized patients with COVID-19 pneumonia.

BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). METHODS: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. RESULTS: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. CONCLUSIONS: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

Do prostate cancer risk models improve the predictive accuracy of PSA screening? A meta-analysis.

BACKGROUND: Despite the extensive development of risk prediction models to aid patient decision-making on prostate screening, it is unknown whether these models could improve predictive accuracy of PSA testing to detect prostate cancer (PCa). The objective of this study was to perform a systematic review to identify PCa risk models and to assess the model's performance to predict PCa by conducting a meta-analysis. DESIGN: A systematic literature search of Medline was conducted to identify PCa predictive risk models that used at least two variables, of which one of the variables was prostate-specific antigen (PSA) level. Model performance (discrimination and calibration) was assessed. Prediction models validated in ≥5 study populations and reported area under the curve (AUC) for prediction of any or clinically significant PCa were eligible for meta-analysis. Summary AUC and 95% CIs were calculated using a random-effects model. RESULTS: The systematic review identified 127 unique PCa prediction models; however, only six models met study criteria for meta-analysis for predicting any PCa: Prostataclass, Finne, Karakiewcz, Prostate Cancer Prevention Trial (PCPT), Chun, and the European Randomized Study of Screening for Prostate Cancer Risk Calculator 3 (ERSPC RC3). Summary AUC estimates show that PCPT does not differ from PSA testing (0.66) despite performing better in studies validating both PSA and PCPT. Predictive accuracy to discriminate PCa increases with Finne (AUC = 0.74), Karakiewcz (AUC = 0.74), Chun (AUC = 0.76) and ERSPC RC3 and Prostataclass have the highest discriminative value (AUC = 0.79), which is equivalent to doubling the sensitivity of PSA testing (44% versus 21%) without loss of specificity. The discriminative accuracy of PCPT to detect clinically significant PCa was AUC = 0.71. Calibration measures of the models were poorly reported. CONCLUSIONS: Risk prediction models improve the predictive accuracy of PSA testing to detect PCa. Future developments in the use of PCa risk models should evaluate its clinical effectiveness in practice.

Recurrent triploidy due to a failure to complete maternal meiosis II: whole-exome sequencing reveals candidate variants.

Triploidy is a relatively common cause of miscarriage; however, recurrent triploidy has rarely been reported. A healthy 34-year-old woman was ascertained because of 18 consecutive miscarriages with triploidy found in all 5 karyotyped losses. Molecular results in a sixth loss were also consistent with triploidy. Genotyping of markers near the centromere on multiple chromosomes suggested that all six triploid conceptuses occurred as a result of failure to complete meiosis II (MII). The proband's mother had also experienced recurrent miscarriage, with a total of 18 miscarriages. Based on the hypothesis that an inherited autosomal-dominant maternal predisposition would explain the phenotype, whole-exome sequencing of the proband and her parents was undertaken to identify potential candidate variants. After filtering for quality and rarity, potentially damaging variants shared between the proband and her mother were identified in 47 genes. Variants in genes coding for proteins implicated in oocyte maturation, oocyte activation or polar body extrusion were then prioritized. Eight of the most promising candidate variants were confirmed by Sanger sequencing. These included a novel change in the PLCD4 gene, and a rare variant in the OSBPL5 gene, which have been implicated in oocyte activation upon fertilization and completion of MII. Several variants in genes coding proteins playing a role in oocyte maturation and early embryonic development were also identified. The genes identified may be candidates for the study in other women experiencing recurrent triploidy or recurrent IVF failure.

Prevalence of thrombocytopenia among patients with chronic hepatitis C: a systematic review.

Thrombocytopenia (TCP) is a haematological condition known to occur in chronically infected hepatitis C (HCV) patients and may interfere with diagnostic procedures, such as liver biopsy, because of risk of bleeding. It may also exclude patients from effective antiviral treatment. We conducted a systematic literature review of articles and conference abstracts, to assess the prevalence of TCP among those with HCV and to describe demographics, liver disease stage and treatment characteristics of these patients. Studies of individuals with confirmed chronic HCV infection were included in the review if the study had a clear definition of thrombocytopenia and a sample size of at least 50 subjects. The final selection included 27 studies (21 articles and six abstracts). The definitions of thrombocytopenia varied between studies and were based either on platelet counts, with threshold levels ranging between ≤ 100 × 10(9) and ≤ 180 × 10(9) /L, or on criteria set in haematological guidelines. The prevalence of TCP ranged from 0.16% to 45.4% and more than half of the studies reported a TCP prevalence of 24% or more. Because of the different TCP definitions, heterogeneity in study design and insufficient data on study characteristics such as age, gender, HCV treatment rates and disease severity an overall summary estimate of TCP prevalence among patients with HCV was not feasible. However, the relatively large prevalence in the majority of the studies suggests that there may be a substantial number of HCV patients at risk of bleeding complications and reduced likelihood of successful HCV antiviral treatment.

Mass spectrometry measurement of a therapeutic peptide for use in multiple sclerosis.

Multiple sclerosis is an autoimmune disease of the central nervous system believed to be mediated by pathogenic T lymphocytes. We have developed a next-generation therapy in which cells secrete specific therapeutic molecules to silence these aberrant T cells. We have shown that fibroblasts, transduced to secrete a myelin basic protein-derived peptide, abrogate disease in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis, which we hypothesized using a low-zone tolerance mechanism. To determine the efficacy (or not) of this therapy in humans, we must ensure that patients receive comparable doses of therapeutic peptide. To this end, we have used liquid chromatography coupled to tandem mass spectrometry to detect a tryptic peptide, derived from the secreted therapeutic product, at nanomolar concentrations. Success depended on growing the transduced fibroblasts in defined PC-1 medium in the presence of a cocktail of protease inhibitors.

Early age at first sexual intercourse and early pregnancy are risk factors for cervical cancer in developing countries.

Early age at first sexual intercourse (AFSI) has long been associated with an increased risk of invasive cervical carcinoma (ICC). Age at first pregnancy (AFP) and ICC have been investigated less, although AFSI and AFP are strongly interrelated in most developing countries. A pooled analysis of case-control studies on ICC from eight developing countries with 1864 cases and 1719 controls investigated the roles of AFSI, AFP, and ICC risk. Age at first sexual intercourse, AFP and age at first marriage (AFM) were highly interrelated and had similar ICC risk estimates. Compared with women with AFSI > or = 21 years, the odds ratio (OR) of ICC was 1.80 (95% CI: 1.50-2.39) among women with AFSI 17-20 years and 2.31 (95% CI: 1.85-2.87) for AFSI < or = 16 years (P-trend <0.001). No statistical interaction was detected between AFSI and any established risk factors for ICC. The ICC risk was 2.4-fold among those who reported AFSI and AFP at < or = 16 years compared with those with AFSI and AFP at > or = 21 years. These data confirm AFSI and AFB as risk factors for ICC in eight developing countries, but any independent effects of these two events could not be distinguished.

Cofilin is an essential component of the yeast cortical cytoskeleton.

We have biochemically identified the Saccharomyces cerevisiae homologue of the mammalian actin binding protein cofilin. Cofilin and related proteins isolated from diverse organisms are low molecular weight proteins (15-20 kD) that possess several activities in vitro. All bind to monomeric actin and sever filaments, and some can stably associate with filaments. In this study, we demonstrate using viscosity, sedimentation, and actin assembly rate assays that yeast cofilin (16 kD) possesses all of these properties. Cloning and sequencing of the S. cerevisiae cofilin gene (COF1) revealed that yeast cofilin is 41% identical in amino acid sequence to mammalian cofilin and, surprisingly, has homology to a protein outside the family of cofilin-like proteins. The NH2-terminal 16kD of Abp1p, a 65-kD yeast protein identified by its ability to bind to actin filaments, is 23% identical to yeast cofilin. Immunofluorescence experiments showed that, like Abp1p, cofilin is associated with the membrane actin cytoskeleton. A complete disruption of the COF1 gene was created in diploid cells. Sporulation and tetrad analysis revealed that yeast cofilin has an essential function in vivo. Although Abp1p shares sequence similarity with cofilin and has the same distribution as cofilin in the cell, multiple copies of the ABP1 gene cannot compensate for the loss of cofilin. Thus, cofilin and Abp1p are structurally related but functionally distinct components of the yeast membrane cytoskeleton.

Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep.

Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.

Gastrointestinal nematode parasites of sheep: a dynamic model for their effect on liveweight gain.

This paper presents an individual-based model for gastrointestinal nematode parasites of sheep and includes the effect of these parasites on the liveweight performance of young sheep. Parasitism is known to affect the host animal in at least two ways. The first induces a loss of appetite in the host, which reduces pasture consumption compared with the parasite-free animal. This effect is examined in the first part of the study. The second major effect of parasitism is a reduction in the metabolic efficiency of the host which decreases nutrients available for maintenance and growth. The latter part of the paper examines the consequences of incorporating this effect on the liveweight changes in individuals in a group of sheep. Previous models addressing this issue have only given mean liveweight and worm burden changes.

Yeast proteins associated with microtubules in vitro and in vivo.

Conditions were established for the self-assembly of milligram amounts of purified Saccharomyces cerevisiae tubulin. Microtubules assembled with pure yeast tubulin were not stabilized by taxol; hybrid microtubules containing substoichiometric amounts of bovine tubulin were stabilized. Yeast microtubule-associated proteins (MAPs) were identified on affinity matrices made from hybrid and all-bovine microtubules. About 25 yeast MAPs were isolated. The amino-terminal sequences of several of these were determined: three were known metabolic enzymes, two were GTP-binding proteins (including the product of the SAR1 gene), and three were novel proteins not found in sequence databases. Affinity-purified antisera were generated against synthetic peptides corresponding to two of the apparently novel proteins (38 and 50 kDa). Immunofluorescence microscopy showed that both these proteins colocalize with intra- and extranuclear microtubules in vivo.

Adaptive Value Normalization in the Prefrontal Cortex Is Reduced by Memory Load.

Adaptation facilitates neural representation of a wide range of diverse inputs, including reward values. Adaptive value coding typically relies on contextual information either obtained from the environment or retrieved from and maintained in memory. However, it is unknown whether having to retrieve and maintain context information modulates the brain's capacity for value adaptation. To address this issue, we measured hemodynamic responses of the prefrontal cortex (PFC) in two studies on risky decision-making. In each trial, healthy human subjects chose between a risky and a safe alternative; half of the participants had to remember the risky alternatives, whereas for the other half they were presented visually. The value of safe alternatives varied across trials. PFC responses adapted to contextual risk information, with steeper coding of safe alternative value in lower-risk contexts. Importantly, this adaptation depended on working memory load, such that response functions relating PFC activity to safe values were steeper with presented versus remembered risk. An independent second study replicated the findings of the first study and showed that similar slope reductions also arose when memory maintenance demands were increased with a secondary working memory task. Formal model comparison showed that a divisive normalization model fitted effects of both risk context and working memory demands on PFC activity better than alternative models of value adaptation, and revealed that reduced suppression of background activity was the critical parameter impairing normalization with increased memory maintenance demand. Our findings suggest that mnemonic processes can constrain normalization of neural value representations.

Radiation survival parameters of antineoplastic drug-sensitive and -resistant human ovarian cancer cell lines and their modification by buthionine sulfoximine.

The optimum integration of chemotherapy and irradiation is of potential clinical significance in the treatment of ovarian cancer. A series of human ovarian cancer cell lines have been developed in which dose-response relationships to standard anticancer drugs have been determined, and the patterns of cross-resistance between these drugs and irradiation have been established. By stepwise incubation with drugs, sublines of A2780, a drug-sensitive cell line, have been made 100-fold, 10-fold, and 10-fold more resistant to Adriamycin (2780AD), melphalan (2780ME), and cisplatin (2780CP). Two additional cell lines, NIH:OVCAR-3nu(Ag+) and NIH:OVCAR-4(Ag+), were established from drug-refractory patients. 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) are all cross-resistant to irradiation, with DOS of 146, 187, 143, and 203, respectively. However, 2780AD remains sensitive to radiation, with a DO of 111, which is similar to that of A2780 (101). Glutathione (GSH) levels are elevated in 2780ME, 2780CP, OVCAR-3nu(Ag+), and OVCAR-4(Ag+) to 4.58, 6.13, 12.10, and 15.14 nmol/10(6) cells as compared to A2780, with 1.89 nmol/10(6) cells. However, the GSH level in 2780AD is only minimally higher than that in A2780 (2.94 nmol/10(6) cells). Buthionine sulfoximine, a specific inhibitor of GSH synthesis, significantly increases the radiation sensitivity of 2780ME (changing the DO from 143 to 95) and 2780CP to a lesser extent, suggesting that intracellular GSH levels may play an important role in the radiation response of certain neoplastic cells. These results suggest that the sequential use of irradiation following chemotherapy with melphalan and cisplatin may be less effective than a combined modality approach, which integrates radiation and chemotherapy prior to the development of drug resistance and cross-resistance to irradiation.

Characterization of a xenograft model of human ovarian carcinoma which produces ascites and intraabdominal carcinomatosis in mice.

We have used in vivo and in vitro procedures to select a subpopulation of cells from the human ovarian carcinoma cell line, NIH:OVCAR-3, with the capacity to grow i.p. in female nude athymic mice. After i.p. injection of these cells, animals develop metastatic spread similar to that of clinical ovarian cancer. Disease progression is characterized by the development of massive ascites, extensive invasive i.p. tumors, and pulmonary metastases. The malignant ascites cells are transplantable, manifest cytoplasmic androgen and estrogen receptors, and express the ovarian cancer associated antigen CA125 (116,000 units/ml of ascites supernatant). The cells also have the same chromosome markers which were present in the original cell line, NIH:OVCAR-3. Survival following i.p. passage of ascites is dependent on tumor cell inoculum ranging from a median survival of 39 days with 40 million cells to 84 days for 11.5 million transplanted cells. The characteristics of this unique in vivo model make it well suited for the evaluation of new drugs and novel experimental therapies in ovarian cancer. In addition, this in vivo model, together with ovarian cancer cell lines, may prove particularly useful for the study of pharmacological ways to specifically increase the cytotoxicity of anticancer agents in tumor cells while not increasing toxicity in normal tissues. The presence of hormone receptors should facilitate the experimental evaluation of hormonal therapy in ovarian cancer.

Characterization of a cis-diamminedichloroplatinum(II)-resistant human ovarian cancer cell line and its use in evaluation of platinum analogues.

Human ovarian cancer cell lines with stable cisplatin resistance have been developed by chronic exposure of the parent cisplatin-sensitive A2780 line to increasing concentrations of cisplatin. 2780CP8 (CP8 refers to this cell line's growth in medium containing 8 microM cisplatin) has several clonal cytogenetic abnormalities but lacks homogeneously staining regions or double-minute chromosomes. It has a significantly greater monolayer growth rate, cloning efficiency in agarose, and total glutathione content compared to the A2780 line, but similar activities of several glutathione-dependent enzymes. The 2780CP8 subline is 7.3-fold resistant to cisplatin compared to the A2780 line, as well as cross-resistant to irradiation and melphalan. It is not cross-resistant to Adriamycin, but this develops with increased cisplatin resistance (14-fold) obtained by further cisplatin exposure of 2780CP8. Of the cisplatin analogues tested which are of current clinical interest, carboplatin, iproplatin, and tetraplatin, only the latter is more cytotoxic than cisplatin in the A2780 and 2780CP8 lines. The 2780CP8 subline is also cross-resistant to these analogues in the relative order carboplatin greater than iproplatin greater than tetraplatin (most to least cross-resistant). Treatment of a highly cisplatin resistant cell line (2780CP70) with either melphalan or cisplatin was associated with a significant increase in [3H]thymidine incorporation into DNA in the presence of 10 mM hydroxyurea compared with the parent sensitive cell line which showed essentially no capacity to repair DNA damage by these drugs. A2780 and its cisplatin-resistant cell lines may thus be useful in studying drug resistance mechanisms, in screening new drugs for activity (especially against drug resistant tumors), and in formulating induction and salvage therapies for ovarian cancer.

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association with MTHFR C677T genotype.

Altered DNA methylation has been previously identified in the spermatozoa of infertile men; however, the origins of these errors are poorly understood. DNA methylation is an epigenetic modification which is thought to play a fundamental role in male germline development. DNA methylation reactions rely on the cellular availability of methyl donors, which are primarily products of folate metabolism, where a key enzyme is methylenetetrahydrofolate reductase (MTHFR). The MTHFR C677T single nucleotide polymorphism (SNP) reduces enzyme activity and may potentially alter DNA methylation processes during germline development. The objective of this study was to determine whether altered DNA methylation in spermatozoa is associated with the MTHFR C677T SNP. DNA methylation was evaluated at the H19, IG-GTL2, and MEST imprinted differentially methylated regions in the spermatozoa of 53 men - 44 oligozoospermic men and nine fertile men with normal sperm parameters via bisulfite sequencing of sperm clones. The 44 infertile men were stratified by severity of oligozoospermia - three normal (>15 million spermatozoa/mL), eight moderate (5-15 million spermatozoa/mL), 23 severe (1-5 million spermatozoa/mL), and 10 very severe (<1 million spermatozoa/mL). MTHFR C677T SNP genotyping was conducted in a subset of 44 peripheral blood samples via restriction fragment length polymorphism. A total of three men - severe oligozoospermic and CT genotype - were found to be altered, which is defined as having ≥50% of their clones altered, where an altered clone was in turn defined as ≥50% of CpGs with incorrect DNA methylation patterns. The incidence of three altered men within the CT subgroup, however, was not significantly higher than the incidence in the CC subgroup. Taken together, altered DNA methylation in spermatozoa was not significantly associated with the MTHFR C677T SNP; however, there was a trend for higher incidence of alterations among severe oligozoospermic infertile men with CT genotypes.

Long-term results of a cisplatin-containing combination chemotherapy regimen for the treatment of advanced ovarian carcinoma.

Sixty-two patients with advanced ovarian adenocarcinoma (stages III and IV) and without prior chemotherapy or radiotherapy were treated with a four-drug combination consisting of cyclophosphamide, hexamethylmelamine, 5-fluorouracil (5-FU), and cisplatin (Chex-UP). All patients were evaluable for toxicity and response, and survivors have been observed for a minimum of 48 months. The overall response rate to Chex-UP chemotherapy was 69%, with 12 patients (19%) achieving a pathologically confirmed complete remission (CR) as documented by a negative second-look laparotomy. Seven of the twelve patients (58%) who achieved a surgically confirmed CR were randomized to six cycles of intraperitoneal (IP) 5-FU. There have been seven relapses in patients who had a negative second-look laparotomy, but only four of the patients died from recurrent ovarian cancer. The median duration of remission following a negative second-look laparotomy was 53 months, while the median duration of survival has not been reached and will exceed 7.5 years. Seventeen patients (27%) achieved a clinical CR with chemotherapy but were found to have residual disease at second-look laparotomy. The median survival for these patients was 29 months, which was statistically inferior to that achieved for those patients with a negative second-look laparotomy (P less than .002), and only one patient is alive after 4 years. All patients who either achieved a partial response (PR) to therapy (14 of 62; 23%) or did not respond to therapy (19 of 62; 31%) died of ovarian cancer by 24 months. Thus, prolonged survival is associated with a surgically confirmed CR to induction therapy with Chex-UP. However, only a minority of advanced-stage ovarian cancer patients (15%) are alive 4 years after initiation of treatment with this regimen.

H-2Ld-alloreactive T cell hybridomas utilize diverse V alpha and V beta T cell receptor chains.

We have sequenced the TCRs from Ld-specific alloreactive T cell hybridomas, whose reactivities we have found to be quite representative of those of a primary dm2 anti-BALB/cJ mixed lymphocyte reaction. We find V beta 6, V beta 7, V beta 8 and V beta 10 gene segments. V alpha usage is diverse, although closely related to that from peptide-specific Ld-restricted CTLs. V alpha-V beta selection provides evidence of preferential pairing. Amino acid frequency analysis shows that the alpha CDR2 region is rich in charged amino acids, in contrast to the beta CDR2 region. Our data suggests the beta chain may be more immunoglobulin-like than the alpha chain, and that charge complementarity may be important in TCR-MHC interactions. We do not consider our results to be contradictory to those previously reported but rather they may represent an early, more diverse response.

Use of liquid crystal thermography in the evaluation of the diabetic foot.

Liquid crystal thermography (LCT) was used to determine temperature variations on the plantar surface of feet. The purpose was to identify thermal emission patterns associated with diabetic foot ulcers. Three population groups were screened: group I, 16 nondiabetic controls; group II, 21 diabetic patients with no history of pedal ulcers; and group III, 28 diabetic patients with active pedal ulceration or history of foot ulcerations. The results demonstrate a generalized increase in plantar foot temperature in group III compared with groups I and II. Temperature readings under metatarsal heads 1-5, great toe, heel, and lateral band were significantly increased (P less than .01) in group III. Additionally, the warm lateral surface displayed by group III patients was not significantly different in temperature from the medial arch of the foot. In groups I and II, the lateral band was significantly cooler (P less than .01) than the medial arch. In group III patients with active ulceration on only one foot, no significant difference in temperature was found between the foot with active ulceration compared with the contralateral nonulcerated foot. When patients with active pedal ulceration were compared with patients with a history of foot ulcers, no significant difference in temperature was seen at five of seven sites tested. A warm concentric color band surrounding active plantar ulcers was identified in group III. This pattern extended from the center of the ulcer to a distance of 8 mm. A significant change in temperature (P less than .01) was noted at 6- and 8-mm distances from the center of the ulcer. In addition, a mottled thermographic pattern was observed more frequently in group III patients than in groups I and II.(ABSTRACT TRUNCATED AT 250 WORDS)