Reconstruction of the Posterolateral Corner of the Knee Using LaPrade and Modified Larson Technique: A Prospective Study

BackgroundPosterolateral corner (PLC) injuries of the knee are often overlooked for its complex anatomy, and frequent association with cruciate ligament injuries. Overlooked injuries lead to reconstruction failure of cruciate ligaments, chronic knee pain and early arthritic changes. Many reconstruction methods are described, but the best treatment still remains elusive. In this study, we have treated grade-III PLC injuries by the ‘anatomic LaPrade’ technique and the ‘fibula-based Modified Larson’ technique, and evaluated their outcomes. Our hypothesis was that both the groups will have similar improvements after surgery.MethodsAn open-label prospective comparative study was done with a total of 28 patients from August 2013 to July 2019. Patients were treated alternatively by LaPrade or Modified Larson technique using hamstring autografts. Follow-up visits were done at sixth week and subsequently at 3, 6, 12, 18 and 24 months postoperatively. Outcomes were measured by Dial Test, side-to-side difference in lateral opening on varus stress radiographs, Lysholm score and IKDC subjective score.ResultsDuring analysis, we considered 25 patients only as three patients were lost to follow-up. Both the groups had comparable improvements in rotational stability, lateral opening on varus stress, Lysholm score and IKDC subjective score.ConclusionBoth LaPrade and Modified Larson technique showed good clinical results in restoring varus and rotational stability of knee in grade-III posterolateral corner injury of the knee.Level of evidenceII (prospective, comparative study)     

Frontal sinus osteomyelitis with midline fistula

Chronic osteomyelitis of frontal sinus is a rare complication of recurrent sinusitis. The pent-up secretions in the sinus may result in pressure necrosis of the containing wall of frontal sinus resulting in persistently discharging fistula. Here we present a case of chronic osteomyelitis of frontal sinus with persistent midline fistula over forehead in a 30 year old male managed surgically by osteoplastic flap procedure and frontal sinus obliteration with abdominal fat.     

Use of RNA interference to prevent lethal murine west nile virus infection

West Nile virus causes fatal encephalitis in humans, mice, and other vertebrates. In the present study, we demonstrate that small interfering RNAs (siRNAs) inhibit West Nile virus replication in vitro. Moreover, the administration of siRNAs to mice by hydrodynamic injection 24 h before challenge with an intraperitoneal inoculum of West Nile virus reduced the viral load and afforded partial protection from lethal infection. These data show the efficacy of the prophylactic use of siRNAs against a viral infection in vivo and suggest new strategies to combat West Nile virus.     

Sigmoid volvulus complicating pregnancy

Sigmoid volvulus complicating pregnancy is an extremely rare complication with fewer than 76 cases reported in literature. We report a case of sigmoid volvulus complicating pregnancy. The sigmoid colon was resected and Hartman's colostomy was performed. The patient had a successful recovery. Aggressive resuscitation followed by early surgical intervention should be undertaken to reduce maternal and fetal morbidity and mortality.     

Insensitivity to the alpha2-adrenergic receptor blocker yohimbine hydrochloride and occurrence of spontaneous platelet macroaggregation (SPMA) in diabetes

We report here a study of platelet aggregation in diabetes, induced by epinephrine and its inhibition by yohimbine hydrochloride (YH), an alpha(2)-adrenergic receptor-blocking agent. Interestingly, emergence of spontaneous platelet macroaggregation (SPMA) was observed in six out of 75 cases in the absence of any agonist. The SPMA cases were strongly associated with insensitivity to YH (in contrast with non-SPMA cases) when epinephrine was used as an agonist. We suggest that the observed correlation is a result of over expression of platelet alpha(2)-adrenoceptors in such subjects. The quantitative nature of the effect is supported by the observation that addition of YH at higher concentration (more than 5 microM) led to restoration of the adrenergic receptor-blocking activity of the said agent. Eventually for non-SPMA subjects YH exhibited blocking activity even at lower concentration. The aggregation profile and the platelet morphology of the SPMA cases had distinctive features as compared to microaggregates formed in other diabetic subjects (non-SPMA cases).     

A study of the temporal course of phenomenology of alcohol dependence

The natural history of alcoholism was first charted out in 1946 by Jellinek, whose original results have been replicated by multiple research groups. They have verified a general progression of alcohol dependence through a series of identifiable phases. The study investigated the sequence of events in the course of alcohol dependence and its deviations from randomness. The study consisted of 36 patients with alcohol dependence, subjected to a structured questionnaire containing 34 items describing the phenomenology of alcohol dependence, based on the lines of SCID. The items experienced by each patient were identified and then plotted on a timeline graph according to an important life event, the items being represented on cards given to the patients randomly. The subjects were re-interviewed after one week and asked to rank their symptoms again to analyze test-retest reliability. The analysis of the item ordering was determined by null hypothesis of randomness. The ordering showed three phases. The early phase was characterized by features of increased tolerance loss of flexibility, and salience. The middle phase consisted mainly of the need for alcohol, and the late phase was predominated by features of physiological withdrawal, tremors, nausea, panics, and hallucinations. There is a characteristic ordering of new events and symptoms, which suggests a developmental process of alcoholism, but this is apparent only if attention is confined to a limited part of the broad spectrum. This process is obscured by consideration of the social concomitants of alcohol dependence. The study of the natural history of alcohol dependence is essential in recognizing and treating the problem and determining whether an intervention appears to be working.     

Miltefosine: An oral drug for visceral leishmaniasis

Miltefosine, a phosphocholine analogue originally developed as antimalignant drug, has been found to be highly active against leishmaniain vitro and animal model. 1,2 Based on these experiences this drug was tried against human visceral leishmaniasis and found to be highly effective and achieved 97% and 94% cure in phase 2 and phase 3 trial in children.     

KLF5 is frequently deleted and down-regulated but rarely mutated in prostate cancer

BACKGROUNDS: Previous studies mapped a region at the q21 band of chromosome 13 (13q21), which is frequently deleted in various human cancers including prostate cancer, suggesting the existence of a tumor suppressor gene at 13q21. The target gene of deletion in prostate cancer, however, has not been identified at present. METHODS: We examined four non-neoplastic and 18 neoplastic prostatic cell lines or xenografts. Homozygous/hemizygous deletion was detected by assays of duplex PCR and real-time PCR. Expression levels of genes were determined by the methods of RT-PCR, real time PCR, and northern blot analysis. Mutations of KLF5 were detected by the approaches of single strand conformational polymorphism (SSCP) and direct sequencing. For the detection of promoter methylation, Southern blotting of genomic DNA and restriction digestion or SSCP analysis of methylation specific PCR products were used. Finally, an expression plasmid of KLF5 was introduced into prostate cancer cell lines with reduced KLF5 expression to investigate colony formation for cell growth. RESULTS: A 2-Mb region of homozygous deletion at 13q21 was detected in the LUCaP70 xenograft of prostate cancer. This region of deletion was further narrowed to 142 Kb by a hemizygous deletion in the NCI-H660 cell line. KLF5 was identified as the only complete gene in the smallest region of deletion. Quantitative deletion of KLF5 genome occurred in six of the 18 (33%) prostate cancer xenografts/cell lines. Each of the six samples with deletion also showed loss of expression for KLF5, suggesting that hemizygous deletion is one mechanism for loss of KLF5 expression. In total, 16 of the 18 cases (89%) showed loss of KLF5 expression at different degrees. In contrast, mutations and promoter methylations were not detected in any of the samples. Functionally, restoration of KLF5 in DU 145 and 22Rv1 cell lines significantly inhibited their growth in vitro. CONCLUSIONS: Frequent genomic deletion and loss of expression as well as cell growth suppression indicate that KLF5 is a reasonable candidate for the tumor suppressor gene at 13q21 in prostate cancer. Mutation and promoter methylation are not common mechanisms for the inactivation of KLF5 in prostate cancer.     

Using small molecules to overcome drug resistance induced by a viral oncogene

We used small molecule screening to discover compounds and mechanisms for overcoming E6 oncogene-mediated drug resistance. Using high-throughput screening in isogenic cell lines, we identified compounds that potentiate doxorubicin's lethality in E6-expressing colon cancer cells. Such compounds included quaternary ammonium salts, protein synthesis inhibitors, 11-deoxyprostaglandins, and two additional classes of compounds-analogs of 1,3-bis(4-morpholinylmethyl)-2-imidazolidinethione (a thiourea) and acylated secondary amines that we named indoxins. Indoxins upregulated topoisomerase IIalpha, the target of doxorubicin, thereby increasing doxorubicin lethality. We developed a photolabeling strategy to identify targets of indoxin and discovered a nuclear actin-related protein complex as a candidate indoxin target.