Transanal endoscopic microsurgery for carcinoma of the rectum

Background The authors present their experience with rectal cancers managed by transanal endoscopic microsurgery (TEM). Methods This prospective study investigated patients undergoing primary TEM excision for definitive treatment of rectal cancer between January 1996 and December 2003 by a single surgeon in a tertiary referral colorectal surgical unit. Results For this study, 52 patients (30 men and 22 women) underwent TEM excision of a rectal cancer. Their mean age was 74.3 years (range, 48–93 years). The median diameter of the lesions was 3.44 cm (range, 1.6–8.5 cm). The median distance of the lesions from the anal verge was 8.8 cm (range, 3–15 cm), with the tumor more than 10 cm from the anal verge in 36 patients. The median operating time was 90 min (range, 20–150 min), and the median postoperative stay was 2 days. All patients underwent full-thickness excisions. There were 11 minor complications, 2 major complications, and no deaths. The mean follow-up period was 40 months (range, 22–82 months). None of the pT1 rectal cancers received adjuvant therapy. Eight patients with pT2 rectal cancer and two patients with pT3 rectal cancer received postoperative adjuvant therapy. The overall local rate of recurrence was 14%, and involved cases of T2 and T3 lesions, with no recurrence after excision of T1 cancers. Three patients died during the follow-up period, but no cancer-specific deaths occurred. Conclusions The findings warrant the conclusion that TEM is a safe, effective treatment for selected cases of rectal cancer, with low morbidity and no mortality. The TEM procedure broadens the range of lesions suitable for local resection to include early cancers (pTis and pT1) and more advanced cancers only in frail people.     

Coincident Kikuchi-Fujimoto’s disease and adult-onset Still’s disease: report of a patient from an uncommonly affected population and case-directed systematic review

Clinical Rheumatology - Kikuchi-Fujimoto's disease (KFD) and adult-onset Still’s disease (AOSD) are rare idiopathic inflammatory conditions of unknown etiology. Ten prior instances of KFD...     

Effect of Colchicine on Platelet-Platelet and Platelet-Leukocyte Interactions: a Pilot Study in Healthy Subjects

The cardioprotective mechanisms of colchicine in patients with stable ischemic heart disease remain uncertain. We tested varying concentrations of colchicine on platelet activity in vitro and a clinically relevant 1.8-mg oral loading dose administered over 1 h in 10 healthy subjects. Data are shown as median [interquartile range]. Colchicine addition in vitro decreased light transmission platelet aggregation only at supratherapeutic concentrations but decreased monocyte- (MPA) and neutrophil-platelet aggregation (NPA) at therapeutic concentrations. Administration of 1.8 mg colchicine to healthy subjects had no significant effect on light transmission platelet aggregation but decreased the extent of MPA (28 % [22–57] to 22 % [19–31], p?=?0.05) and NPA (19 % [16–59] to 15 % [11–30], p?=?0.01), platelet surface expression of PAC-1 (370 mean fluorescence intensity (MFI) [328–555] to 333 MFI [232–407], p?=?0.02) and P-selectin (351 MFI [269–492] to 279 [226–364], p?=?0.03), and platelet adhesion to collagen (10.2 % [2.5–32.6] to 2.0 % [0.2–9.5], p?=?0.09) 2 h post-administration. Thus, in clinically relevant concentrations, colchicine decreases expression of surface markers of platelet activity and inhibits leukocyte-platelet aggregation but does not inhibit homotypic platelet aggregation.     

Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia

Objective

Treatment resistance is a challenge for the management of schizophrenia. It is not always clear whether inadequate response is secondary to medication ineffectiveness, as opposed to medication underexposure due to non‐adherence or pharmacokinetic factors. We investigated the prevalence of subtherapeutic antipsychotic plasma levels in patients identified as treatment‐resistant by their treating clinician.

Method

Between January 2012 and April 2017, antipsychotic plasma levels were measured in 99 individuals provisionally diagnosed with treatment‐resistant schizophrenia by their treating clinicians, but not prescribed clozapine. Patients were followed up to determine whether they were subsequently admitted to hospital.

Results

Thirty‐five per cent of plasma levels were subtherapeutic, and of these, 34% were undetectable. Black ethnicity (P = 0.006) and lower dose (P < 0.001) were significantly associated with subtherapeutic/undetectable plasma levels. Individuals with subtherapeutic/undetectable levels were significantly more likely to be admitted to hospital (P = 0.02).

Conclusion

A significant proportion of patients considered treatment‐resistant have subtherapeutic antipsychotic plasma levels, and this is associated with subsequent admission. The presence of subtherapeutic plasma levels may suggest a need to address adherence or pharmacokinetic factors as opposed to commencing clozapine treatment. While antipsychotic levels are not recommended for the routine adjustment of dosing, they may assist with the assessment of potential treatment resistance in schizophrenia.     

Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins

We have adopted an idiotypic approach to study the double stranded DNA (dsDNA) binding antibodies of systemic lupus erythematosus (SLE). Three anti-idiotypic reagents, 8.12, 3I, and F4, identify cross reactive idiotypes that are each expressed on anti-dsDNA antibodies in the sera of many patients with SLE. These idiotypic antibodies are implicated in the pathogenesis of SLE as they are present in immune complex deposits in the kidneys of patients with SLE glomerulonephritis. The autoantibody associated idiotypes are also expressed on antibodies that do not bind DNA. We are investigating the origin of the pathogenic anti-dsDNA antibodies of SLE by comparing the autoantibodies, the antibodies to foreign antigens, and the myeloma proteins that express each SLE associated idiotype. In conjunction with serological analysis of these idiotypic systems, molecular genetic studies indicate that both the 8.12 and the 3I autoantibody associated idiotypes may be germline encoded, while the F4 idiotype is generated by somatic mutation. The data further suggest that the antigenic specificity of the pathogenic anti-DNA antibodies of SLE is acquired through somatic mutation of germline immunoglobulin genes. By studying the regulation of genes capable of encoding pathogenic autoantibodies, in both SLE patients and non-autoimmune individuals, we may be able to elucidate the pathogenesis of autoimmune disease and begin to design more effective therapeutic interventions.     

The neutrophil: function and regulation in innate and humoral immunity

The neutrophil is a critical effector cell in humoral and innate immunity and plays vital roles in phagocytosis and bacterial killing. Discussed here are the neutrophil components necessary for these processes and the diseases in which these components are either lacking or dysfunctional, illustrating that normal neutrophil function is vital for health.     

Nitric oxide synthases and osteoarthritis

The production of nitric oxide (NO) by chondrocytes is increased in human osteoarthritis. The excessive production of NO inhibits matrix synthesis and promotes its degradation. Furthermore, by reacting with oxidants such as superoxide anion, NO promotes cellular injury and renders the chondrocyte susceptible to cytokine-induced apoptosis. Thus, NO produced by activated chondrocytes in diseased cartilage may modulate disease progression in osteoarthritis and should therefore be considered a potential target for therapeutic intervention.     

Update on gout: Pathophysiology and potential treatments

After several decades of senescence, the twin fields of hyperuricemia and gout have again regained attention in both the scientific and clinical spheres, and this review highlights several recent advancements. Specifically, we review newly discovered mechanisms of uric acid-induced inflammation, uric acid’s putative role as a “danger signal” in innate immunity, the possible link between hyperuricemia and cardiovascular disease, and evolutionary evidence suggesting that hyperuricemia conferred a survival advantage in primates (when the gene for uricase was lost) several million years ago. Finally, we provide an overview of the current approach to gout, as well as what treatments are on the horizon.