Respiratory Syncytial Virus Infects the Bonnet Monkey, Macaca radiata

The Bonnet monkey model of respiratory syncytial virus (RSV) infection may be a useful nonhuman primate model for studying RSV disease in humans because Bonnet monkeys can predictably be infected to obtain an orderly sequence of morphologic, cytologic, virologic, serologic, and inflammatory changes related to time of infection. Young feral Bonnet monkeys, Macaca radiata, were infected endotracheally with 10⁶ plaque-forming units (pfu) of the Long strain of RSV. RSV was recovered from the animals' lungs at necropsy on days 3, 5, and 7 with the highest viral titer obtained on day 3 (1.1 and 5.2 × 10³ pfu/g of tissue in the upper and lower lobes, respectively). RSV antigen and F protein mRNA were detected 3–5 days after infection in alveolar macrophages and in the epithelium of bronchi, terminal bronchioles, and alveoli. Histologic analysis of RSV-infected lungs at necropsy revealed progressive bronchiolar mucosal and submucosal inflammation, periarterial mononuclear interstitial inflammation, and focal alveolitis, with a maximal response at 7 days after infection. Cell counts in bronchoalveolar lavage (BAL) increased with time with neutrophils and macrophages predominating on day 3 (6.47 and 5.85 × 10⁵/mm³, respectively) and lymphocytes predominating on day 9 (4.18 × 10⁵/mm³). Serum-neutralizing antibody appeared on day 5 and IgG antibody to RSV was detected on day 9. This sequence of morphologic, cytologic, virologic, serologic, and inflammatory change following RSV infection creates a useful model in the study of experimentally induced RSV disease with a potential for testing future vaccine-induced alterations in RSV disease response. Received March 20, 1998; accepted September 7, 1998.     

Controlled clinical trial of a regimen of two durations for the treatment of isoniazid resistant pulmonary tuberculosis

Patients with pulmonary tuberculosis who were failures of primary chemotherapy with strains resistant to isoniazid or to isoniazid and streptomycin were allocated at random to receive a regimen of rifampicin and ethambutol for 6 (4RE) or 9 months (7RE), supplemented in both treatment series by streptomycin plus pyrazinamide for the first 2 months. The patients were treated in hospital for the first 2 months and thereafter treatment was supervised on a daily basis in the nearest health institution by an appointed member of staff or at home by responsible members of the community. A total of 306 patients was admitted and 226 patients remained for analysis at the end of chemotherapy, 179 with a strain resistant to isoniazid alone and 47 with a strain resistant to isoniazid and streptomycin. There were only two failures at the end of chemotherapy, one in the 6-month series who had resistance to both isoniazid and streptomycin pretreatment, and one in the 9-month series who had resistance to isoniazid alone. For the 144 patients with initial resistance to isoniazid alone assessed up to 30 months, the relapse rates were low in both series: 4% for the 72 patients in the 6-month series and 3% for the 72 patients in the 9-month series. However, for the 34 patients with resistance to both drugs, three of the 14 in the 6-month but none of 20 in the 9-month series relapsed.     

Antileishmanial, antiplasmodial and cytotoxic activities of 12,16-dideoxy aegyptinone B from Zhumeria majdae Rech.f. & Wendelbo

The ethanol extract of Zhumeria majdae showed potent antileishmanial and antiplasmodial activity in vitro. Bioactivity guided fractionation of the extract led to the isolation of 12,16-dideoxy aegyptinone B. This compound exhibited potent in vitro antileishmanial activity with an IC(50) of 0.75 microg/mL and a strong antiplasmodial activity with IC(50) values of 1.3 and 1.4 microg/mL against chloroquine sensitive and resistant strains, respectively. This compound was further found to have mild cytotoxicity towards cancer cell lines.     

Long circulating lipid nanocapsules for drug detoxification

Uncoated and poly(ethylene glycol) (PEG)-decorated lipid nanocapsules (NC) prepared from medium chain triglycerides were investigated both in vitro and in vivo as parenteral detoxifying colloids for their ability to sequester haloperidol, docetaxel and paclitaxel. In vitro studies showed that the uptake depended on the nature of the drug and the composition of NC core and shell. In the case of haloperidol, maximal affinity was achieved upon incorporation of a complexing fatty acid. In plasma lipoprotein distribution studies, the association of both haloperidol and docetaxel into triglyceride-rich lipoprotein fraction was significantly increased in the presence of NC. The ability of the NC to lower the free drug concentrations in incubation medium was confirmed by cytotoxicity studies, where the antiproliferative activity of docetaxel was significantly decreased in the presence of NC. Using docetaxel as drug model, the NC were finally evaluated for their uptake potential in mice by one of the following administration sequences between the drug solution (Taxotere, DTX) and NC: NC-DTX, PEG(NC)-DTX and DTX-PEG(NC). Irrespective of the administration sequence, the NC increased the blood levels of docetaxel due to the in situ sequestration of drug by the circulating carrier. These findings suggest that lipid NC could be used as a non-specific mode to deal with the sequestration of molecules with high affinity for oils.     

Clinical features and surgical outcomes of complications of proliferative diabetic retinopathy in young adults with type 1 diabetes mellitus versus type 2 diabetes mellitus - A comparative observational study

Purpose:To evaluate the clinical profile, visual outcomes, and complications among young adult patients with type 1 diabetes mellitus (insulin-dependent DM-T1DM) in comparison with patients with type 2 diabetes mellitus (T2DM) undergoing vitrectomy for complications of proliferative diabetic retinopathy (PDR).Methods:A retrospective review of patients between 18 and 45 years with T1DM undergoing vitrectomy for complications of PDR between June 2017 and June 2019, with a minimum follow-up of 12 months. Consecutive patients between 30 and 45 years with type 2 diabetes (non-insulin-dependent DM-T2DM) who underwent vitrectomy for the same indications were retrospectively enrolled as the control group.Results:There were 42 eyes (28 patients) in the T1DM group and 58 eyes (47 patients) in the T2DM group. The average age at operation was 35.9 ± 6.88 years and 39.8 ± 3.03 years, respectively (P < 0.001). At the end of follow-up, the mean logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 1.53 ± 0.55 to 1.30 ± 0.93 (P value 0.07) in the T1DM group and from 1.59 ± 0.46 to 1.00 ± 0.78 in the T2DM group (P = 0.0001). The rate of the primary and final reattachment was 76.2% and 88.1% in the T1DM group and 84.5% and 96.6% in the T2DM group. Preoperative macular tractional retinal detachment (MTRD) and neovascular glaucoma (NVG) in both the groups, chronic kidney disease (CKD) and lack of preoperative Pan retinal photocoagulation (PRP) in the T1DM group, hypertension (HTN) and, resurgery in the T2DM group, were risk factors for poor vision at the final follow-up.Conclusion:The visual and anatomic outcomes were poorer in the T1DM patients which could be due to the longer duration of diabetes with worse glycemic control, associated comorbidities like CKD, and a higher incidence of MTRD.     

Surgical outcome of full-thickness macular hole secondary to tractional retinal detachment in proliferative diabetic retinopathy

Purpose:To evaluate the surgical outcome of full-thickness macular hole (FTMH) secondary to active fibrovascular proliferation (FVP) and tractional retinal detachment (TRD) in eyes with proliferative diabetic retinopathy (PDR), and factors influencing the outcome.Methods:This retrospective study included the patients who underwent vitrectomy for FTMH secondary to PDR TRD from 2016 to 2020. Anatomical and visual outcomes were analyzed after six months along with the factors predicting the final outcome and duration of subretinal fluid (SRF) resolution.Results:Group A (macula-off combined RD, i.e., tractional and rhegmatogenous) included 10 eyes, while group B (macula-threatening TRD) included eight eyes. The mean best-corrected visual acuity improved from logMAR 1.21 (Snellen equivalent: 20/324) to logMAR 0.76 (Snellen equivalent: 20/115) (P = 0.008). Seventeen patients gained ≥1 line(s) of vision. Mean visual gain in groups A and B was 3.7 ± 1.9 and 1.9 ± 1.1 lines, respectively (P = 0.051). MH closed in 88.9% eyes. Type 1 anatomical closure was achieved in 88.9% of eyes. At 6 months, SRF and central macular thickness reduced from 479.6 ± 512.5 μm to 11.4 ± 23.5 μm (P = 0.002) and 874.3 ± 422.6 μm to 207.6 ± 81.7 μm (P = 0.0002), respectively. Finally, macular SRF resolved in all the patients. The mean duration for complete SRF resolution was 4.9 ± 3.2 months. Eyes with a shorter duration of diabetes mellitus (rho = −0.49, P = 0.040) and macula-off combined RD (P = 0.048) took a longer time for complete SRF resolution.Conclusion:Good anatomical and visual outcomes can be achieved in eyes with PDR TRD-associated FTMH. The residual macular SRF resolves slowly after the surgery and extra intervention is not required. Macula-off combined RD is associated with worse outcome and a slower SRF resolution rate.     

Modifiable risk factors remain significant causes of medium term mortality after first time Coronary artery bypass grafting

Postoperative bleeding might become a serious problem in the management of cardiac surgical patients, with marked medical and economic impact. In these life-threatening situations, massive haemorrhage represents frequently a combination of surgical and coagulopathic bleeding. Surgical bleeding results from a definite source at the operation site and can be corrected using surgical standard techniques. Acute coagulopathies, in contrast, result from impaired thrombin formation, and require optimized therapeutical strategies. Effective pharmacological treatment will be complicated by the presence of ventricular assist devices (VAD), which necessarily imply effective anticoagulation. In episodes of uncontrolled coagulopathic bleeding, the application of recombinant activated factor VII (rFVIIa) as a effective haemostatic agent has become more and more popular. However, only very few data are available on its use in patients with VAD in place. We researched the PubMed-database for case reports about the use of rFVIIa in patients with VAD and summarized them. In addition, we report a case from our hospital. In all cases cessation of bleeding without any thrombembolic complications could be achieved. In cases of uncontrollable, non-surgical bleeding rFVIIa seems to be a therapeutical option even for patients with VAD.