Subtype‐specific differences in transmission cluster dynamics of HIV‐1 B and CRF01_AE in New South Wales,Australia

IntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.     

Effects of Electroconvulsive Therapy on the Electrocardiogram in Geriatric Patients with Stable Cardiovascular Diseases

Eight elderly patients (mean age +/- SD, 73.2 +/- 9.5 years) were studied with Holter electrocardiographic monitoring for 24 h before and 24 h after an electroconvulsive therapy (ECT) treatment. Patients with a history of cardiac disease but who were not experiencing any active cardiac symptoms were chosen for study. They were not receiving either cardioactive medications or psychotropic agents that can effect cardiac rhythm or conduction. Each patient served as his own control, with direct comparison of the periods before and after the treatment. There were no differences before and after ECT in the electrocardiogram. One minute after the seizure, patients were hypertensive and tachycardic. ECT does not appear to pose additional risk in stable, elderly patients with a history of cardiac disease.     

Reconstruction of male external genitalia with elephantiasis

The surgical rehabilitation of a patient with severely deformed and functionally disabled genitalia due to long-standing lymphedema and infection is described and illustrated. The term "elephantiasis" has been applied to such gross lesions. Appropriate surgery to the penis, scrotum, and perineum has yielded a gratifying result. The principles and techniques of the surgical approach in such an undertaking are presented and discussed.     

Chloramphenicol toxicity associated with severe cardiac dysfunction

Summary A 9-month-old infant experienced severe chloramphenicol toxicity associated with high serum levels (313 g/ml). Cardiovascular collapse with cardiomyopathic changes and impaired left ventricular function was documented by echocardiography. Serial echocardiographic evaluation showed resolution of the cardiomyopathic findings as the chloramphenicol levels were spontaneously cleared. Clinical course was complicated by the development of liver disease and coagulopathy compatible with disseminated intravascular consumption. Patient's recovery was complete and uneventful, nevertheless, chloramphenicol toxicity in childhood is associated with a significant mortality rate of 40%. The related impaired cardiac function, although reversible, appears to play a major role in the pathogenesis and eventual outcome in this syndrome.     

Levels of expression of CYR61 and CTGF are prognostic for tumor progression and survival of individuals with gliomas.

The biological properties of CCN proteins include stimulation of cell proliferation, migration, and adhesion, as well as angiogenesis and tumorigenesis. We quantified CYR61, CTGF, WISP-1, and NOV mRNA expression levels in samples from sixty-six primary gliomas and five normal brain samples using quantitative real-time PCR assay. Statistical analysis was performed to explore the links between expression of the CCN genes and clinical and pathological parameters. Overexpression of CYR61, CTGF, WISP-1, and NOV occurred in 48% (32 of 66), 58% (38 of 66), 36% (24 of 66), and 15% (10 of 66) of primary gliomas, respectively. Interestingly, significant associations were found between CYR61 expression versus tumor grade, pathology, gender, and age at diagnosis. Also, a significant correlation existed between CTGF mRNA levels versus tumor grade, gender, and pathology. In contrast to CYR61 and CTGF, no significant association was found between expression of either WISP-1 or NOV versus any of the pathological features. Furthermore, Cox regression analysis showed that CYR61 and CTGF expression had a significant correlation with patient survival. These results suggest that CYR61 and CTGF may play a role in the progression of gliomas; their levels at diagnosis may have prognostic significance; and these proteins might serve as valuable targets for therapeutic intervention.     

Thalidomide metabolites in mice and patients with multiple myeloma.

PURPOSE:This research examines the profile of metabolites of thalidomide that are formed in refractory multiple myeloma patients undergoing thalidomide therapy in comparison with those that are detected in healthy mice. EXPERIMENTAL DESIGN: Urine or plasma samples from patients during thalidomide therapy (100-400 mg daily), or from mice treated i.p. (100 mg/kg) or p.o. with thalidomide (50 mg/kg) were analyzed using liquid chromatography-mass spectrometry. Metabolites in each of the peaks observed in the UV- and mass spectrometry-detected high-performance liquid chromatography traces were identified by comparison of retention times and spectra with those of authentic standards. RESULTS: Plasma and urine samples from mice 4 h after treatment with thalidomide contained eight major metabolites formed by hydroxylation and/or hydrolysis of thalidomide. In contrast, urine samples from seven multiple myeloma patients at steady state levels of thalidomide therapy showed the presence of only three hydrolysis breakdown products and no hydroxylated metabolites. CONCLUSIONS: Our results show that thalidomide metabolite profiles in multiple myeloma patients differ considerably from those in mice. The lack of measurable hydroxylated metabolites in urine and in 1 case plasma of these patients suggests that such metabolites are not responsible for the therapeutic effects of thalidomide in multiple myeloma. We suggest that thalidomide may act directly, down-regulating growth factors essential for multiple myeloma growth.     

Review of Percutaneous Tracheostomy

The purpose of this study is to assess the safety and efficacy of the four known methods of percutaneous tracheostomy. Perioperative, postoperative, and late complication rates were generated for each method after a complete literature review identified 1684 percutaneous tracheostomy patients reported in 40 series. Two methods, the Toye and the guide wire dilator forceps (GWDF) methods, have been the subject of few investigations. Two other methods have been extensively studied. A high perioperative complication rate was calculated for the Rapitrac? method, whereas percutaneous dilational tracheostomy (PDT) has complication rates similar to those reported for standard operative tracheostomy. A retrospective review of 22 patients who underwent PDT at a local community hospital confirmed a “learning curve” for this technique that had been previously suggested. Review of the literature suggests that PDT can be safe and cost-effective for selected patients, but a learning curve for this technique exists that dictates caution, experience, and preparation on the part of any surgeon who wishes to add percutaneous tracheostomy to his or her repertoire.