Improvement in Hidradenitis Suppurativa and quality of life in patients treated with adalimumab: Real-world results from the HARMONY Study.

BACKGROUND: Hidradenitis suppurativa (HS), a chronic, recurrent, debilitating skin disease, is characterized by painful, inflammatory, subcutaneous lesions of the axilla, inguinal and anogenital regions. Overall prevalence of HS is ˜1%, and the impact of disease on patient quality of life (QoL) and healthcare resource utilization (HRU) is high. OBJECTIVES: To estimate the real-world effectiveness of adalimumab (Humira®) treatment in patients with moderate-to-severe HS on disease severity, pain, QoL, work productivity and HRU. METHODS: HARMONY (Effectiveness of Adalimumab in Moderate to Severe HidrAdenitis SuppuRativa Patients - a Multi-cOuNtry studY in Real Life Setting) is a multicentre, postmarketing observational study in adult patients with moderate-to-severe HS. Disease severity and QoL parameters were evaluated using validated measures at 12-week intervals over 52 weeks of treatment. The primary endpoint was the proportion of patients achieving a Hidradenitis Suppurativa Clinical Response (HiSCR: ≥50% reduction in abscess and inflammatory nodule count, with no increase in abscess and draining fistula counts relative to baseline) at 12 weeks. Secondary endpoints were HiSCR at 24, 36 and 52 weeks and changes in QoL parameters and work productivity assessments. Analyses were conducted using as-observed data. RESULTS: The proportion of patients reaching the primary HiSCR endpoint was 70.2% (n = 132/188 enrolled) and remained ≥70% until study completion. There were statistically significant (P < 0.0001) reductions in worst and average skin pain. All of the QoL measures evaluated improved significantly (P < 0.0001) by 12 weeks of adalimumab treatment, as did work productivity assessments (P < 0.05), and there was a ˜50% decrease in HRU between baseline and week 52. Adalimumab was well tolerated. CONCLUSIONS: In this real-world setting, adalimumab treatment of moderate-to-severe HS resulted in decreased disease severity and improvements in QoL and productivity. Response to adalimumab was rapid (within 12 weeks) and sustained (52 weeks). No unexpected safety signals were reported.

When Azoles Cannot Be Used: The Clinical Effectiveness of Intermittent Liposomal Amphotericin Prophylaxis in Hematology Patients.

BACKGROUND: Patients unable to take azoles are a neglected group lacking a standardized approach to antifungal prophylaxis. We evaluated the effectiveness and safety of intermittent liposomal amphotericin B (L-AMB) prophylaxis in a heterogenous group of hematology patients. METHODS: A retrospective cohort of all hematology patients who received a course of intravenous L-AMB, defined as 1 mg/kg thrice weekly from July 1, 2013 to June 30, 2018, were identified from pharmacy records. Outcomes included breakthrough-invasive fungal disease (BIFD), reasons for premature discontinuation, and acute kidney injury. RESULTS: There were 198 patients who received 273 courses of L-AMB prophylaxis. Using a conservative definition, the BIFD rate was 9.6% (n = 19 of 198) occurring either during L-AMB prophylaxis or up to 7 days from cessation in patients who received a course. Probable/proven BIFD occurred in 13 patients (6.6%, 13 of 198), including molds in 54% (n = 7) and non-albicans Candidemia in 46% (n = 6). Cumulative incidence of BIFD was highest in patients with acute myeloid leukemia (6.8%) followed by acute lymphoblastic leukemia (2.7%) and allogeneic stem cell transplantation (2.5%). The most common indication for L-AMB was chemotherapy, or anticancer drug-azole interactions (75% of courses) dominated by vincristine, or acute myeloid leukemia clinical trials, followed by gut absorption concerns (13%) and liver function abnormalities (8.8%). Acute kidney injury, using a modified international definition, complicated 27% of courses but was not clinically significant, accounting for only 3.3% (9 of 273) of discontinuations. CONCLUSIONS: Our findings demonstrate a high rate of BIFD among patients receiving L-AMB prophylaxis. Pragmatic trials will help researchers find the optimal regimen of L-AMB prophylaxis for the many clinical scenarios in which azoles are unsuitable, especially as targeted anticancer drugs increase in use.

Mental health and caregiving experiences of family carers supporting people with psychosis.

AIMS: Family carers supporting an individual with psychosis often experience poorer mental health, however, little is known about specific risk factors among these carers. We investigated the associations between demographic, caregiving characteristics and mental health outcomes in family carers supporting an individual with psychosis and compared carers' outcomes with general population norms. METHODS: We analysed baseline data from the COPe-support randomised controlled trial of online psychoeducation and peer support for adult carers supporting an individual with psychosis between 2018 and 2020. We collected carers' demographic and health outcome data, including wellbeing using Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS as primary outcome), quality of life using EQ-5D-5L and caregiving experience assessed with Experience of Caregiving Inventory. We tested associations between carers' demographic and caregiving characteristics for each outcome in turn and meta-analysed carers' WEMWBS and EQ-5D-5L with Health Survey England (HSE) general population data from 2016 and 2017, respectively. RESULTS: The 407 carers of people with psychosis had a mean WEMWBS score of 42.2 (s.d. 9.21) and their overall weighted pooled WEMWBS score was 7.3 (95% confidence interval (CI) -8.6 to -6.0, p < 0.01) lower than the HSE general population sample, indicating carers have poorer mental wellbeing by more than double the minimum clinically important difference of 3 points on WEMWBS. Among all caring relationships, partners had poorer wellbeing compared to parents with lower WEMWBS score (-6.8, -16.9 to 3.3, p = 0.03). Single carers had significantly poorer wellbeing (-3.6, -5.6 to -1.5, p < 0.01) and a more negative caregiving experience than those who were cohabiting. Spending more than 35 h per week caregiving increased carers' negative experience significantly (p = 0.01). CONCLUSION: Carers of people with psychosis have poorer mental health than non-carers. Partners, lone carers and those spending more than 35 h per week on caring were found to be most at risk of poor mental health. Based on the results, we advocate that the details of carers for individuals with psychosis should be added to the existing carers or severe mental illness registers at all general practitioner surgeries and for their wellbeing screened routinely. Future large-scale prospective studies are needed to develop a predictive model to determine risk factors, hence to aid early identification of carers' support needs. Such understandings are also useful to inform tailored intervention development.

Anergic T cells as suppressor cells in vitro.

T cell-mediated suppression is an established phenomenon, but its underlying mechanisms are obscure. An in vitro system was used to test the possibility that anergic T cells can act as specific suppressor cells. Anergic human T cells caused inhibition of antigen-specific and allospecific T cell proliferation. In order for the inhibition to occur, the anergic T cells had to be specific for the same antigen-presenting cells (APCs) as the T cells that were suppressed. The mechanism of this suppression appears to be competition for the APC surface and for locally produced interleukin-2.

Significant frequencies of T cells with indirect anti-donor specificity in heart graft recipients with chronic rejection.

BACKGROUND: The purpose of this study was to determine whether T cells with indirect allospecificity could be detected in heart transplant recipients with chronic rejection. METHOD AND RESULTS: Human T-cell clones were used to determine the most effective way to deliver major histocompatibility complex alloantigens for indirect presentation. Seven allograft recipients with evidence of progressive, chronic rejection were selected. Four heart graft recipients with no evidence of chronic rejection were used as controls. Peripheral blood T cells and antigen-presenting cells from the recipients were cultured with frozen/thawed stored donor cells or major histocompatibility complex class I-derived synthetic peptides in limiting dilution cultures and then compared with controls using tetanus toxoid and frozen/thawed third-party cells with no human leukocyte antigens in common with the donor. In 5 of 7 patients analyzed who had chronic rejection, elevated frequencies of T cells with indirect, anti-donor specificity (iHTLf) were detected. No such elevated iHTLf were detected in recipients without chronic rejection. DISCUSSION: iHTLf can be obtained from human transplant recipients, which supports the contention that the indirect pathway is involved in chronic transplant rejection.

A rapid limiting dilution assay for measuring frequencies of alloreactive, interleukin-2-producing T cells in humans.

A limiting dilution analysis (LDA) has been established which measures the total numbers of alloreactive interleukin-2 (IL-2)-secreting T cells in human peripheral blood mononuclear cells (PBMC). A significant advantage over most previous LDA is that the assay may be completed in approximately 48 h since an IL-2-dependent 'indicator' cell line is used to reduce assay time. Results are reproducible and correlate with the degree of HLA class II antigenic disparity between responder and stimulator cells. Use of both PBMC and Epstein-Barr virus-transformed B lymphoblastoid cell lines (B-LCL) as stimulator cells permits estimation of the frequency of Epstein-Barr virus-specific T cells in different responder individuals. A modification of the assay may also be used to measure the frequencies of 'primed' alloreactive cells, i.e., those alloreactive cells which have previously encountered their specific stimulating alloantigen. Use of the assay in the clinical context of bone marrow and renal transplantation is discussed.

Malaria among United States troops in Somalia.

PURPOSE: United States military personnel deployed to Somalia were at risk for malaria, including chloroquine-resistant Plasmodium falciparum malaria. This report details laboratory, clinical, preventive, and therapeutic aspects of malaria in this cohort. PATIENTS AND METHODS: The study took place in US military field hospitals in Somalia, with US troops deployed to Somalia between December 1992 and May 1993. Centralized clinical care and country-wide disease surveillance facilitated standardized laboratory diagnosis, clinical records, epidemiologic studies, and assessment of chemoprophylactic efficacy. RESULTS: Forty-eight cases of malaria occurred among US troops while in Somalia; 41 of these cases were P falciparum. Risk factors associated with malaria included: noncompliance with recommended chemoprophylaxis (odds ratio [OR] 2.4); failure to use bed nets (OR 2.6); and failure to keep sleeves rolled down (OR 2.2). Some patients developed malaria in spite of mefloquine (n = 8) or doxycycline (n = 5) levels of compatible with chemoprophylactic compliance. Five mefloquine failures had both serum levels > or = 650 ng/mL and metabolite:mefloquine ratios over 2, indicating chemoprophylactic failure. All cases were successfully treated, including 1 patient who developed cerebral malaria. CONCLUSIONS: P falciparum malaria attack rates were substantial in the first several weeks of Operation Restore Hope. While most cases occurred because of noncompliance with personal protective measures or chemoprophylaxis, both mefloquine and doxycycline chemoprophylactic failures occurred. Military or civilian travelers to East Africa must be scrupulous in their attention to both chemoprophylaxis and personal protection measures.

Measurement of cytotoxic T lymphocyte precursor frequencies reveals cryptic HLA class I mismatches in the context of unrelated donor bone marrow transplantation.

BACKGROUND: In this large, two-center study, 260 cytotoxic T lymphocyte precursor (CTLp) frequency assays, performed to assess patient-donor compatibility, were analyzed in relation to the degree of HLA matching. METHODS: While the tissue-typing techniques used at the Royal Postgraduate Medical School (RPMS) and Anthony Nolan Bone Marrow Trust (ANBMT) differ, the results of the analyses on the two sites are analogous, with high CTLp frequencies (>1:100,000) in 42% and 41% of recipient-donor pairs, respectively. RESULTS: Recipient-donor combinations with class I mismatches and class II identity were associated with high CTLp frequencies (collectively 83% vs. 17% low CTLp). This correlation was not as strong in pairs where class II mismatches were demonstrated (61% high vs. 39% low). Despite using different matching procedures, the RPMS and ANBMT both show that 32% of the "perfectly" matched pairs (i.e., where no mismatch was detected by any of the techniques used here) had high frequencies of recipient-specific CTLp. CONCLUSIONS: The failure of conventional methods to identify such a level of histoincompatibilities indicates that the CTLp assay has an important role in the selection of unrelated donors for bone marrow transplantation.

Optimizing a limiting dilution culture system for quantifying the frequency of interleukin-2-producing alloreactive T helper lymphocytes.

BACKGROUND: The development of sensitive, specific, and reproducible techniques to quantify T cells with direct allospecificity has potential applications in the selection of bone marrow donors and in the monitoring of the antidonor alloresponse in patients after organ transplantation. Such data may provide an objective basis for altering existing immunosuppression, monitoring novel antirejection therapies, and predicting long-term graft outcome. We have previously published a correlation between donor antirecipient T helper frequencies (HTLf) and the severity of acute graft-versus-host disease after bone marrow transplantation. Using the same assay protocol, we have described the development of donor-specific hyporesponsiveness in a proportion of renal transplant recipients. However, several imperfections existed in the protocols used in these studies. Cellular interactions within the stimulator and the responder cell populations, and back stimulation of T cells within the stimulator cell population, could give rise to extraneous interleukin-2 and alter the validity or estimation of derived recipient antidonor HTLf. METHODS: Using peripheral blood mononuclear cells as the responding population and splenic mononuclear cells as the stimulating population, we have examined the possible effects of these cellular interactions on the results of limiting dilution analysis assays for HTLf measurement. RESULTS: These interactions have the ability to alter the validity or estimation of HTLf. We show that by depleting the responder population of HLA class II+ cells and depleting T cells from the stimulating population, these interactions are effectively abrogated. CONCLUSIONS: On the basis of the findings reported here, we describe an optimized HTLf assay which is sensitive, specific, and reproducible. This has obvious applications in the analysis of alloimmune responses in transplantation.

The relationship between MHC restricted and allospecific T cell recognition.

The existence in the mature T cell repertoire of a high precursor frequency of cells which recognise allogeneic MHC molecules appears to contradict the well-established dogma of positive selection for self MHC restriction. In order to explore the possibility that alloreactive cells are derived from a fraction of the repertoire that is not self-MHC-restricted, the contribution of in vivo-primed T cells to "primary" alloresponses was investigated. Peripheral blood T cells were separated into virgin and memory populations by sorting for low and high levels of LFA-3 expression, and their proliferative responses to MHC incompatible stimulator cells was quantitated. The results demonstrated that approximately half of a "primary" alloresponse is contributed by previously primed T cells that, by definition, must be self-MHC restricted. Furthermore it was possible to define the original MHC-restricted antigen specificity of two T cell clones raised against the allospecific HLA-DR1 from a DR4Dw4/DRw13DW19 responder. The emerging consensus view that anti-MHC alloreactive T cells, like antigen-specific T cells, are specific for MHC/peptide complexes, and have a parental self-MHC restriction, begs a structural explanation. Comparison of multiple DR beta 1 domain sequences reveals that DR molecules fall into groups that have extensive homology in the residues on the beta 1 domain alpha-helix that are predicted to point up towards the T cell receptor (histotopic), and thus to determine MHC restriction. Given that the DR alpha chain is invariant this creates the possibility that anti-DR allorecognition can mimic self-restricted recognition. Within these groups of histotopically similar DR products there are multiple differences in the peptide-binding residues that lie on the inner aspects of the alpha-helix or on the floor of the antigen-binding groove. As a consequence, it is predicted that a different array of endogenous peptides will be bound, due to determinant selection. Thus, allorecognition within these groups may result from the recognition of endogenous peptides that are bound by stimulator but not by responder MHC products, seen in a self-restricted manner. In combinations where histotopic similarity does not exist, allorecognition may be best explained by the chance occurrence of a receptor selected for intermediate affinity for thymically expressed MHC molecules having a higher affinity for an allogeneic histotope. Such a receptor would have been deleted in a thymus expressing the allospecificity, but would be perceived as "safe" in the absence of this MHC product.

Use of a murine T-cell hybridoma expressing human T-cell receptor alpha- and beta-gene products as a tool for the production of human T-cell receptor-specific monoclonal antibodies.

We describe the production of mouse monoclonal antibodies specific for the human TcR using as the immunogen transfected murine T-cell hybridoma cells coexpressing mouse CD3 with human Jurkat TcR alpha and beta chains. The shortage of monoclonal antibodies (mAbs) specific for the human TcR-V alpha and V beta families reflects the difficulties in their production by conventional methods using whole human T cells or purified soluble receptors as immunogens. As an alternative strategy to circumvent these difficulties, we have generated a transfected mouse T-cell line expressing a human (Jurkat) TcR alpha beta dimer in a complex with mouse CD3. The parental mouse T-cell line, TG40, is a cell surface TcR-negative, cytoplasmic CD3-positive variant of the mouse T-cell hybridoma 2B4. The human-TcR alpha beta expressing mouse transfectant was used to immunize mice with the same genetic background as the parent mouse T-cell line, and a human TcR-specific response was successfully achieved. MAb-producing hybridomas were generated by fusing spleen cells from the immunized mice with the mouse myeloma cell line NSO. Of 124 hybridoma supernatants screens, 72 showed reactivity to the human T-cell line Jurkat. Twenty-four of the hybridomas producing human (Jurkat) TcR-specific antibodies were cloned and screened for reactivity to Jurkat TcR. Several IgG2b and IgM mAbs specific for the Jurkat T cell line were selected on the basis of their ability to modulate surface CD3 expression on Jurkat cells. Most of the antibodies do not stain other TcR-expressing human T cell leukemia cell lines, implying specificity for the variable domains of the Jurkat TcR.(ABSTRACT TRUNCATED AT 250 WORDS)

Orthotopic liver transplantation for hepatic GVHD following allogeneic BMT for chronic myeloid leukaemia.

A 21-year-old man who had an HLA-identical sibling donor BMT for chronic myeloid leukaemia developed grade IV acute GVHD of the liver that was unresponsive to corticosteroids and anti-IL2 receptor monoclonal antibody. He was treated with an orthotopic liver transplant and is currently well 6 months later with normal liver function and no evidence of GVHD in the transplanted liver.

Diarrheal disease among military personnel during Operation Restore Hope, Somalia, 1992-1993.

The potential for widespread diarrheal disease was regarded as a substantial threat to U.S. troops participating in the early phases of Operation Restore Hope in Somalia. Outpatient surveillance of 20,859 U.S. troops deployed during the first eight weeks, however, indicated that a mean of only 0.8% (range 0.5-1.2%) of personnel sought care for diarrhea each week, and in three epidemiologic surveys, < 3% of troops reported experiencing a diarrheal illness per week. Despite these low overall attack rates, diarrhea accounted for 16% of 381 hospital admissions and 20% of 245 patients admitted with a temperature > or = 38.5 degrees C. Sixty-one specimens were obtained from inpatients and 52 were obtained from outpatients. Shigella sp. were isolated from 33%, enterotoxigenic Escherichia coli from 16%, Giardia lamblia from 4%, and rotavirus from 1% of 113 stool samples obtained from inpatient (61) and outpatient (52) troops with diarrhea. Bacterial isolates obtained in Somalia were resistant to doxycycline (78%), ampicillin (54%), and sulfamethoxazole (49%), but uniformly sensitive to ciprofloxacin. With the exception of 10 Shigella sonnei isolates that were linked epidemiologically to one eating facility, bacterial pathogens occurred sporadically and demonstrated a wide variation of serotypes and antibiotic sensitivity patterns. Additionally, three of 11 paired sera collected from persons with nausea, vomiting, and watery diarrhea demonstrated a four-fold or greater increase in titer to Norwalk virus antibody. These data indicate that large outbreaks of diarrheal disease did not occur; however, highly drug-resistant enteric bacteria, and to a lesser extent viral and parasitic pathogens, were important causes of morbidity among U.S. troops in Somalia.

Dengue fever in U.S. troops during Operation Restore Hope, Somalia, 1992-1993.

Dengue fever (DF) was considered to be a potential cause of febrile illness in U.S. troops deployed to Somalia during Operation Restore Hope in 1992-1993. A prospective study of hospitalized troops with fever and a seroepidemiologic survey of 530 troops were conducted. Among 289 febrile troops hospitalized, 129 (45%) did not have an identified cause of their fever. Dengue (DEN) virus was recovered from 41 (43%) of 96 of these patients by inoculation of admission sera into C6/36 cell cultures. Thirty-nine (41%) of the isolates were identified as DEN-2 and two (2%) as DEN-3 by an indirect immunofluorescent antibody assay. An additional 18 (49%) of 37 culture-negative cases were shown by immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay to have anti-DEN virus antibody. All identified DF cases recovered within 1-2 weeks; no case of dengue hemorrhagic fever or shock syndrome was observed. A seroepidemiologic survey of a unit (n = 494) with 17 culture or serologically identified DF cases and a 13% attack rate of unidentified febrile illness revealed a 7.7% prevalence of anti-DEN virus IgM antibody. Failure to use bed nets was the only identified risk factor for DEN infection (adjusted odds ratio = 2.2, 95% confidence interval = 1.4-3.0). These data indicate that DF was an important cause of febrile illness among US troops in Somalia, and demonstrate the difficulties in preventing DEN infection in troops operating in field conditions.

Etiology of acute diarrhea among United States military personnel deployed to South America and west Africa.

A study of acute diarrhea was conducted from 1985 to 1987 among U.S. military personnel participating in routine shipboard exercises in South America and West Africa and ground troops deployed to coastal Ecuador. An enteropathogen was identified in 146 (51%) of 289 acute cases of diarrhea. Enterotoxigenic Escherichia coli, found in 50 (17%) patients with diarrhea, was the most commonly identified enteropathogen. Viral enteropathogens were also found in a high percentage of acute cases of diarrhea: rotavirus was detected in 11% of the patients and Norwalk virus infection in 10%. Most enteric pathogens were acquired in equal frequencies in South America and West Africa, except for rotavirus infection which was identified more often in West Africa and enteroaggregative E. coli infection which was identified more often in South America. Bacterial enteropathogens were frequently resistant to trimethoprim/sulfamethoxazole, but no resistance to quinolone drugs was observed, indicating that quinolone drugs have become important agents for the treatment of diarrhea in South America and West Africa.

Nontoxigenic 01 Vibrio cholerae in Peru: a report of two cases associated with diarrhea.

Two 01 Vibrio cholerae, E1 Tor strains, serogroup Ogawa were isolated from diarrheal stool material of two North American males residing or visiting in Peru. No other enteric pathogens were found. These strains did not produce cholera toxin as detected by enzyme-linked immunosorbent and Y1 adrenal cell assays, nor did they hybridize with an oligonucleotide probe for heat-labile (LT) toxin of Escherichia coli. These two cases are the first reports of 01 V. cholerae isolated from clinical specimens in South America.

Syntheses and Vibrational and (13)C MAS-NMR Spectra of Bis(carbonyl)mercury(II) Undecafluorodiantimonate(V) ([Hg(CO)(2)][Sb(2)F(11)](2)) and of Bis(carbonyl)dimercury(I) Undecafluorodiantimonate ([Hg(2)(CO)(2)][Sb(2)F(11)](2)) and the Molecular Structure of [Hg(CO)(2)][Sb(2)F(11)](2).

The synthesis of bis(carbonyl)mercury(II) undecafluorodiantimonate(V), [Hg(CO)(2)][Sb(2)F(11)](2), and that of the corresponding mercury(I) salt [Hg(2)(CO)(2)][Sb(2)F(11)](2) are accomplished by the solvolyses of Hg(SO(3)F)(2) or of Hg(2)F(2), treated with fluorosulfuric acid, HSO(3)F, in liquid antimony(V) fluoride at 80 or 60 degrees C, respectively, in an atmosphere of CO (500-800 mbar). The resulting white solids are the first examples of metal carbonyl derivatives formed by a post-transition element. Both salts are characterized by FT-IR, FT-Raman, and (13)C-MAS-NMR spectroscopy. For [Hg(CO)(2)][Sb(2)F(11)], unprecedentedly high CO stretching frequencies (nu(av) = 2279.5 cm(-)(1)) and stretching force constant (f(r) = 21.0 +/- 0.1) x 10(2) Nm(-)(1)) are obtained. Equally unprecedented is the (1)J((13)C-(199)Hg) value of 5219 +/- 5 Hz observed in the (13)C MAS-NMR spectrum of the (13)C labeled isotopomers at delta = 168.8 +/- 0.1 ppm. The corresponding values (nu(av) = 2247 cm(-)(1), f(r) = (20.4 +/- 0.1) x 10(2) Nm(-)(1), (1)J((13)C-(199)Hg) = 3350 +/- 50 Hz and (2)J((13)C-(199)Hg) 850 +/- 50 Hz) are found for [Hg(2)(CO)(2)][Sb(2)F(11)](2), which has lower thermal stability (decomposition point in a sealed tube is 140 degrees C vs 160 degrees C for the Hg(II) compound) and a decomposition pressure of 8 Torr at 20 degrees C. The mercury(I) salt is sensitive toward oxidation to [Hg(CO)(2)][Sb(2)F(11)](2) during synthesis. Both linear cations (point group D(infinity)(h)()) are excellent examples of nonclassical (sigma-only) metal-CO bonding. Crystal data for [Hg(CO)(2)][Sb(2)F(11)](2): monoclinic, space group P2(1)/n; Z = 2; a = 7.607(2) Å; b = 14.001(3) Å; c = 9.730(2) Å; beta = 111.05(2) degrees; V = 967.1 Å(3); T = 195 K; R(F) = 0.035 for 1983 data (I(o) >/= 2.5sigma(I(o))) and 143 variables. The Hg atom lies on a crystallographic inversion center. The Hg-C-O angle is 177.7(7) degrees. The length of the mercury-carbon bond is 2.083(10) Å and of the C-O bond 1.104(12) Å respectively. The structure is stabilized in the solid state by a number of significant secondary interionic Hg- - -F and C- - -F contacts.

Conformational preferences in glycosylamines. implications for the exo-anomeric effect.

The conformational preferences about the C-N bond in N-(4-methoxyphenyl)-2,3,4,6-tetra-O-acetyl-alpha (1) and beta-D-glucopyranosylamine (2), in the solid state and in solution, have been investigated. The crystal structure of the axially substituted alpha anomer (1) indicates a conformational preference about the C-1-N bond in which nN-->sigma*C-O exo-anomeric interactions may be expressed, although this conformational preference is not displayed in solution. The solution conformation relieves steric interactions that result from expression of the exo-anomeric effect in the solid-state conformation. The conformational preference in the equatorially substituted beta anomer (2) both in solution and in the solid state is similar and permits expression of nN-->sigma*C-O exo-anomeric interactions. The structural data for 1 and 2 indicate significant differences in O-5-C-1-N-1 bond angles but insignificant differences in each of the O-5-C-1 or C-1-N-1 bond lengths. The J(C-1-H-1 coupling constants in 1 and 2 indicate a greater coupling constant for the alpha anomer that is consistent with a dominant nO-->sigma*C-H orbital interaction in the beta anomer that weakens the C-1-H-1 bond.