Intralesional immunotherapy with killed Mycobacterium w vaccine for the treatment of ano-genital warts: an open label pilot study

Background  Intralesional immunotherapy with skin test antigens and vaccines has been found to be effective in the management of genital and extragenital warts.
Objective  To evaluate the efficacy and safety of intralesional Mycobacterium w (M w ) vaccine monotherapy for the treatment of ano-genital warts.
Patients and methods  Ten patients clinically diagnosed to have external ano-genital warts, including three with giant ano-genital warts (Buschke Löwenstein tumour), were included in this open-label pilot study. Two patients were human immunodeficiency virus seropositive, and one was on iatrogenic immunosuppression for renal transplantation. M w vaccine (0.1 mL) was initially injected intradermally in the deltoid region on both the sides, followed 2 weeks later by intradermal intralesional injection into the genital warts. Intralesional injections were repeated weekly until either complete clearance or a maximum of 10 injections was achieved.
Results  One patient was lost to follow-up after the first intralesional injection. In 8 out of remaining 9 patients (88.9%), the genital warts cleared completely. In one patient with giant perianal wart, the lesion was reduced to less than 5% of its volume after 10 intralesional injections, which was later electrosurgically excised. The treatment was well tolerated by the majority of the patients. The adverse reactions were noted in four patients, which were reversible. No recurrence was seen after a mean follow-up of 5.1 months.
Conclusion  Intralesional immunotherapy of ano-genital warts with M w vaccine seems to be a promising new approach, which needs to be evaluated in the randomized controlled trials.     

Internal fixation and muscle pedicle bone grafting in femoral neck fractures

Background:

The treatment of displaced intracapsular femoral neck fracture is still an unsolved problem. Non-union and avascular necrosis are the two main complications of this fracture, especially if patient presents late. Muscle pedicle bone grafting has been advocated to provide additional blood supply. We present analysis of our 32 cases of displaced femoral neck fracture treated by internal fixation and quadratus femoris based muscle pedicle bone grafting.

Materials and Methods:

Open reduction and internal fixation with muscle pedicle grafting was done in 32 patients. The age of patients varied from 14-62 years (average age 45 years) with male to female ratio of 13:3. Twenty-nine fractures were more than three weeks old. All the cases were treated by Meyers'' procedure. The fracture was internally fixed after open reduction and then a muscle pedicle graft was applied. It was supplemented by cancellous bone graft in seven cases. Fixation was done by parallel cancellous lag screws (n = 19), crossed Garden''s screws (n = 7), parallel Asnis screws (n = 5) and Moore''s pin (n = 1).Quadratus femoris muscle pedicle graft was used in 32 cases. In the initial 12 cases the graft was fixed with circumferential proline sutures, but later, to provide a secure fixation, the graft was fixed with a cancellous screw (n = 20). Postoperative full weight bearing was deferred to an average of 10 weeks.

Results:

Union was achieved in 26/29 (89.65%) cases which could be followed for an average period of 3.4 years, (2-8.5 years) with good functional results and had the ability to squat and sit cross-legged. Results were based on hip rating system given by Salvatti and Wilson. The results were excellent in 15 cases, good in four cases, fair in four cases and poor in six cases. Complications were avascular necrosis (n = 2), transient foot drop (n = 2), coxa-vara (n = 1) and temporary loss of scrotal sensation (n = 1).

Conclusion:

Muscle pedicle bone grafting with internal fixation is a viable treatment option in displaced femoral neck fractures with late presentation.     

Sildenafil in pediatric pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children.KEY WORDS: Child, phosphodiesterase (PDE)-5 inhibitor, Pulmonary hypertension therapy     

ANEURYSM OF SINUS OF VALSALVA DISSECTING INTO THE INTERVENTRICULAR SEPTUM – ECHOCARDIOGRAPHIC DIAGNOSIS (A Case Report)

Aneurysm of sinus of Valsalva dissecting into interventricular septum is a rare entity. We report one such case who was incidentally diagnosed by echocardiography to have this abnormality during evaluation of a clinically suspected isolated aortic regurgitation.KEY WORDS: Aneurysm – dissecting – sinus of Valsalva, Echocardiography     

Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhinovirus 3C protease inhibitor

The picornavirus 3C protease is required for the majority of proteolytic cleavages that occur during the viral life cycle. Comparisons of published amino acid sequences from 6 human rhinoviruses (HRV) and 20 human enteroviruses (HEV) show considerable variability in the 3C protease-coding region but strict conservation of the catalytic triad residues. Rupintrivir (formerly AG7088) is an irreversible inhibitor of HRV 3C protease with potent in vitro activity against all HRV serotypes (48 of 48), HEV strains (4 of 4), and untyped HRV field isolates (46 of 46) tested. To better understand the relationship between in vitro antiviral activity and 3C protease-rupintrivir binding interactions, we performed nucleotide sequence analyses on an additional 21 HRV serotypes and 11 HRV clinical isolates. Antiviral activity was also determined for 23 HRV clinical isolates and four additional HEV strains. Sequence comparison of 3C proteases (n = 58) show that 13 and 11 of the 14 amino acids that are involved in side chain interactions with rupintrivir are strictly conserved among HRV and HEV, respectively. These sequence analyses are consistent with the comparable in vitro antiviral potencies of rupintrivir against all HRV serotypes, HRV isolates, and HEV strains tested (50% effective concentration range, 3 to 183 nM; n = 125). In summary, the conservation of critical amino acid residues in 3C protease and the observation of potent, broad-spectrum antipicornavirus activity of rupintrivir highlight the advantages of 3C protease as an antiviral target.     

A prospective study of symptomatic bacteremia following platelet transfusion and of its management

BACKGROUND: The danger of bacteremia due to contaminated platelets is not well known. There are also no established guidelines for the management of febrile reactions after platelet transfusion. STUDY DESIGN AND METHODS: To determine the risk of symptomatic bacteremia after platelet transfusion, 3584 platelet transfusions given to 161 patients after bone marrow transplantation were prospectively studied. Platelet bags were routinely refrigerated for 24 hours after transfusion. Septic work-up was initiated for a temperature rise of more than 2 degrees C above the pretransfusion value within 24 hours of platelet transfusion or a temperature rise of more than 1 degree C that was associated with chills and rigor. Diagnosis of bacteremia after platelet transfusion was made only when the pairs of isolates from the blood and the platelet bags were identical with respect to their biochemical profile, antibiotic sensitivity, serotyping, or ribotyping. RESULTS: Thirty-seven febrile reactions, as defined above, occurred. Bacteremia subsequent to platelet transfusion was diagnosed in 10 cases. There was a 27-percent chance (95% CI, 15–43%) that these febrile reactions represented bacteremia that resulted from platelet transfusion. For a subgroup of 19 patients with a temperature rise of more than 2 degrees C, the risk of bacteremia was 42 percent (95% CI, 23–64%). Septic shock occurred in 4 of the 10 bacteremic patients. A rapid diagnosis was possible because the involved bacteria were demonstrated by direct Gram stain of the samples taken from the platelet bags of all 10 patients. CONCLUSION: Significant febrile reactions after platelet transfusion are highly likely to be indicative of bacteremia. Routine retention of platelet bags for subsequent microbiologic study was useful in the investigation of these febrile reactions. Empiric antibiotic therapy is indicated.