Treatment of end-stage diabetic nephropathy: over a decade of experience at one institution

Results of treatment of end-stage renal disease in 139 patients with diabetes mellitus revealed survival of 76% at 1 year and 48% at 5 years. These results compare favorably with other reports from Europe and the United States, probably because of the greater number of patients receiving renal transplants, and possibly because of the use of continuous ambulatory peritoneal dialysis as a recent treatment modality. Patients not receiving transplants were much older (mean age, 47.8 years) than those receiving transplants. Of those not given transplants, survival was best on CAPD. Comparison of those surviving at least 3 years was made with those expiring in the first year. Long-term survivors were younger, had diabetes for a shorter period, but had higher mean blood pressures and serum creatinine values than short-term survivors. Short-term survivors also had over a 50% incidence of prior myocardial infarction or cardiorespiratory arrest, while no long-term survivors had such a history. Long-term survivors were also more likely to have received a transplant, and short-term survivors were more likely to have received intermittent peritoneal dialysis or hemodialysis. A transplant from a living related donor is the treatment of choice for diabetics under age 40 and perhaps for older patients as well. The choice among CAPD, hemodialysis and cadaver transplant requires consideration of many factors.     

Transforming growth factor beta contributes to lung leak in rats given interleukin-1 intratracheally

Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute lung injury (ALI) and administering recombinant human IL-1alpha (rhIL-1alpha) (50 ng) intratracheally causes an acute, neutrophil-dependent, oxidative lung leak in rats that closely resembles human ALI. In the present work, the authors tested the hypothesis that transforming growth factor beta (TGFbeta) contributes to the lung inflammation and injury that develops in rats given IL-1 intratracheally. They found that intravenous administration of a monoclonal antibody to TGFbeta (1.D.11.16, 0.5 mg/kg) attenuated lung injury responses, specifically lung leak index, lung lavage protein concentrations, and blood oxygenation abnormalities, that are observed 5 hours after intratracheal instillation of IL-1 in rats, but did not decrease indices of lung inflammation, specifically myeloperoxidase (MPO) activity in lung tissue, neutrophil counts in lung lavage, and cytokine-induced neutrophil chemoattractant (CINC) levels in lung lavage, in rats given IL-1 intratracheally. The results suggest that TGFbeta contributes to lung leak, but not lung inflammation, following intratracheal administration of IL-1 in rats.     

Epidemiologic and clinical features of endemic Campylobacter jejuni infection in Bangladesh

Epidemiologic and clinical features of infection with Campylobacter jejuni in Bangladesh were examined in (1) diarrheal patients infected with C jejuni, (2) healthy control subjects, and (3) village children who were cultured monthly and at each diarrheal episode during a 10-month period. C jejuni was isolated from 437 (14%) of 3,038 outpatients with diarrhea. These patients had no distinct clinical presentation and were more likely to have a mixed infection than were patients infected with other pathogens (59% vs 42%, P less than 0.01). Age-specific infection rates were greatest in infants and did not differ significantly from those in control subjects. C jejuni was isolated less frequently from village children with diarrhea than from those cultured routinely (5% vs 9%, P less than 0.05). Forty percent of 47 patients with C jejuni vs 23% of 48 control subjects (P less than 0.01) had an elevated convalescent-phase antibody titer as determined by complement fixation test. In Bangladesh, enteric infection with C jejuni is common but often asymptomatic, although pathogenicity is suggested by serologic response in some patients.     

Ileus caused by obstructing colorectal cancer—impact on long-term survival

Purpose

It is unclear whether obstructing colorectal cancer (CRC) has a worse prognosis than non-obstructing CRC. Of CRC patients, 10–28% present with symptoms of acute obstruction. Previous studies regarding obstruction have been primarily based on short-term outcomes, risk factors and treatment modalities. With this study, we want to determine the long-term survival of patients presenting with acute obstructive CRC.

Methods

This single-centre observational retrospective cohort study includes all CRC patients who underwent surgery between December 2004 and 2010. Patients were divided into two groups: ileus and no ileus. Survival analyses were performed for both groups. Additional survival analyses were performed in patients with and without synchronous metastases. The primary outcome was survival in months.

Results

A total of 1236 patients were included in the analyses. Ileus occurred in 178 patients (14.4%). The 5-year survival for patients with an ileus was 32% and without 60% (P?<?0.01). In patients without synchronous metastases, survival with and without an ileus was 40.9 and 68.4%, respectively (P?<?0.01). If ileus presentation was complicated by a colon blowout, 5-year survival decreased to 29%. No significant difference was found in patients with synchronous metastases. Survival at 5 years in this subgroup was 10 and 12% for patients with and without an ileus, respectively (P?=?0.705).

Conclusions

Patients with obstructive CRC have a reduced short-term overall survival. Also, long-term overall survival is impaired in patients who present with acute obstructive CRC compared to patients without obstruction.

     

Public attitudes and opinions toward physicians and dentists infected with bloodborne viruses: results of a national survey

BACKGROUND: There has been no recent assessment of public attitudes and opinions concerning risk of bloodborne virus transmission during health care. METHODS: Seven items in the 2000 annual Healthstyles survey were used to assess current attitudes and opinions about health care providers infected with human immunodeficiency virus (HIV) and the risk of bloodborne virus transmission during health care in a sample of approximately 3000 US households. RESULTS: Of the 2353 respondents, 89% agreed that they want to know whether their doctor or dentist is infected with HIV; 82% agreed that disclosure of HBV or HCV infection in a provider should be mandatory. However, 47% did not believe that HIV-infected doctors were more likely to infect patients than doctors infected with HBV or HCV. Opinions were divided on whether HIV-infected providers should be able to care for patients as long as they use good infection control: only 38% thought that infected providers should be allowed to provide patient care. CONCLUSIONS: These findings suggest that improved public education and risk communication on health care-associated bloodborne infections is needed.     

Comparison of tissue Doppler and propagation velocity to invasive measures for measuring left ventricular filling pressures

The utility of tissue Doppler and propagation velocity in identifying patients with abnormal left ventricular filling pressures was assessed in 50 patients who underwent catheterization and echocardiography on the same day. The ratios of the peak velocity of early mitral inflow to early mitral annular velocity (E/Ea) and the velocity of propagation (E/Vp) were compared with invasive measurements of pre-A-wave left ventricular pressures. Echocardiography measures were 77% to 92% accurate in identifying patients with a pre-A-wave pressure >15 mm Hg. Tissue Doppler imaging is more accurate than propagation velocity.     

Longitudinal analysis of alcohol consumption and health of middle-aged women in Australia

Aims To assess the prospective association between alcohol consumption and self‐rated health: in particular whether there is a relationship between stable alcohol intake and health; whether health is affected by changes in alcohol consumption; whether having a chronic condition alters the relationships between stable and changing alcohol intake and health; and whether the health of longer‐term abstainers is different from more recent and intermittent abstainers. Design Longitudinal analysis of a prospective, population‐based study. Setting Australia. Participants A total of 13 585 randomly selected 45–50‐year‐old women surveyed in 1996, of whom 9396 (69%) were resurveyed in 1998, 2001 and 2004. Measurements Estimates for the General Health subscale of the SF‐36 for different levels of alcohol intake adjusted for having a chronic condition, depression, smoking and other factors. Findings Longitudinal models of consistent alcohol intake showed mean scores for general health of moderate drinkers were significantly better than that of non‐drinkers [mean difference = 4.3, standard error (SE) = 0.61], occasional drinkers (mean difference = 3.1, SE = 0.52) and heavy drinkers (mean difference = 2.1, SE = 1.00). Among moderate drinkers, a decrease or variation in alcohol consumption was associated with a significant decline of three to four points in general health. Similar results were obtained when women with an existing chronic condition were excluded from these models. The health of recent abstainers and intermittent drinkers was the same as longer‐term abstainers. Conclusions Consistent moderate drinkers had the best health even after adjustment for having a chronic condition, depression and life‐style factors. Poorer health was associated with decreased alcohol intake among occasional and moderate drinkers.     

Effects of TSH receptor mutations on binding and biological activity of monoclonal antibodies and TSH.

The effects of an extensive series of mutations in the TSH receptor (TSHR) leucine-rich domain (LRD) on the ability of thyroid-stimulating monoclonal antibodies (TSMAbs) and TSH to bind to the receptor and stimulate cyclic AMP production in TSHR-transfected CHO cells has been investigated. In addition, the ability of a mouse monoclonal antibody with blocking (i.e., antagonist) activity (RSR-B2) to interact with mutated receptors has been studied. Several amino acids distributed along an extensive part of the concave surface of the LRD were found to be important for binding and stimulation by the thyroid-stimulating human MAb M22 but did not appear to be important for TSH binding and stimulation. Most of these amino acids important for M22 interactions were also found to be important for the stimulating activity of six different mouse TSMAbs and a hamster TSMAb. Furthermore, most of these same amino acids were important for stimulation by TSHR autoantibodies in a panel of sera from patients with Graves' disease. Amino acid R255 was the only residue found to be unimportant for TSH stimulation but critical for stimulation by all thyroid-stimulating antibodies tested (23 patient serum TSHR autoantibodies, M22, and all seven animal TSMAbs). About half the amino acids (all located in the N-terminal part of the LRD) found to be important for M22 activity were also important for the blocking activity of RSR-B2 and although the epitopes for the two MAbs overlap they are different. As the two MAbs have similar affinities, their epitope differences are probably responsible for their different activities. Overall our results indicate that different TSMAbs and different patient sera thyroid-stimulating autoantibodies interact with the same region of the TSHR, but there are subtle differences in the actual amino acids that make contact with the different stimulators.     

Simultaneous analysis of 29 synthetic cannabinoids and metabolites,amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs‐of‐abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs‐of‐abuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported‐liquid‐extraction (SLE) followed by liquid chromatography?tandem mass spectrometry (LC?MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante‐ and post‐mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB‐FUBINACA and/or acid (61%), 5F‐ADB and/or acid (40%), ADB‐FUBINACA (11%), 5F‐MDMB‐PICA acid (6%), and MDMB‐FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.     

Macroautophagy in lymphatic endothelial cells inhibits T cell–mediated autoimmunity

Lymphatic endothelial cells (LECs) present peripheral tissue antigens to induce T cell tolerance. In addition, LECs are the main source of sphingosine-1-phosphate (S1P), promoting naive T cell survival and effector T cell exit from lymph nodes (LNs). Autophagy is a physiological process essential for cellular homeostasis. We investigated whether autophagy in LECs modulates T cell activation in experimental arthritis. Whereas genetic abrogation of autophagy in LECs does not alter immune homeostasis, it induces alterations of the regulatory T cell (T reg cell) population in LNs from arthritic mice, which might be linked to MHCII-mediated antigen presentation by LECs. Furthermore, inflammation-induced autophagy in LECs promotes the degradation of Sphingosine kinase 1 (SphK1), resulting in decreased S1P production. Consequently, in arthritic mice lacking autophagy in LECs, pathogenic Th17 cell migration toward LEC-derived S1P gradients and egress from LNs are enhanced, as well as infiltration of inflamed joints, resulting in exacerbated arthritis. Our results highlight the autophagy pathway as an important regulator of LEC immunomodulatory functions in inflammatory conditions.