Efficacy and Mid Term Results of Lateral Parapatellar Approach Without Tibial Tubercle Osteotomy for Primary Total Knee Arthroplasty in Fixed Valgus Knees

The lateral parapatellar approach, despite providing direct access to the pathological area has not been widely accepted for knee arthroplasty in valgus deformities. We performed a modified lateral (Keblish) approach which consisted of coronal z plasty of lateral retinaculum, quadriceps snip, titrated sequential lateral release and closure with expanded lateral structures in 32 arthritic fixed valgus knees. In 30 knees, either tendon of popliteus or lateral collateral ligament or both could be preserved. At an average follow-up of 5 years, the valgus alignment improved from 25.4° (11°–60°) to 4° (0°–10°) and knee society score improved from 34 to 95 points. There was no late instability or revisions. This approach is rational, eliminates patella maltracking, is applicable in severe deformities and with titrated release, can preserve the posterolateral knee stabilizers that are necessary for long term implant survival.     

Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C.

PURPOSE: N-Benzoyl staurosporine (PKC412) is a protein kinase C inhibitor with antitumor activity in laboratory models. We determined the toxicity of oral PKC412 administered daily for repeat cycles of 28 days. PATIENTS AND METHODS: Thirty-two patients with advanced solid cancers were treated at seven dose levels (12.5 to 300 mg daily) for a total of 68 cycles. RESULTS: The most frequent treatment-related toxicities were nausea, vomiting, fatigue, and diarrhea. At the two top dose levels (225 and 300 mg/d), 15 of 16 patients experienced nausea/vomiting (common toxicity criteria [CTC], version 1), grade 2 in nine of 16 and grade 3 in three of 16 patients; and six of 16 patients developed CTC grade 2 diarrhea. After 1 month of treatment, there were significant reductions in circulating lymphocyte (P <.02) and monocyte (P <.01) counts in patients receiving doses > or = 100 mg/d. Nevertheless, only two patients developed myelosuppression (both grade 2). Of two patients with progressive cholangiocarcinoma, one attained stable disease lasting 4.5 months and one a partial response lasting 4 months. There was a linear relationship between PKC412 dose and area under the curve (0-24 hours) and maximum plasma concentration with marked interpatient variability. The estimated median elimination half-life was 1.6 days (range, 0.9 to 4.0 days), and a metabolite with a median half-life of 36 days was detected. Steady-state PKC412 plasma levels at the top three dose cohorts (150 to 300 mg) were five to 10 times the cellular 50% inhibitory concentration for PKC412 of 0.2 to 0.7 micromol/L. CONCLUSION: PKC412 can be safely administered by chronic oral therapy, and 150 mg/d is suitable for phase II studies. The pharmacokinetics and lack of conventional toxicity indicate that pharmacodynamic measures may be additionally needed to optimize the drug dose and schedule.     

Longitudinal study of β2-microglobulin abnormalities in schizophrenia

In an earlier cross-sectional study, we reported antipsychotic-naive schizophrenia patients to have significantly elevated β2-microglobulin (β2M) level suggestive of its potential association with the pathogenesis of schizophrenia. In this study, we present the follow-up analyses of β2M in 31 patients from the previous study who were re-assessed after 92.1 ± 7.2 days of antipsychotic treatment. Compared to baseline, there was a further significant elevation of β2M in schizophrenia patients following treatment, especially in those who were treated with risperidone. Also, there was a significant negative correlation between β2M level and total psychopathology score during follow-up in risperidone group. The study findings extend further support the role for β2M in the pathogenesis of schizophrenia strengthening the case for immune dysregulation. Moreover, the observations suggest the possibility that the mechanism of action of antipsychotics might involve alteration of immune parameters.     

Causes and management of pulmonary air leak in newborns

Pulmonary air leaks are usually complications of mechanical ventilation, although they can occur spontaneously. The reported incidence varies from 1% in term infants to 20% in preterm infants. The incidence has decreased in recent years. Ventilatory manoeuvres which increase mean airway pressure are associated with increased air leaks. Use of higher ventilatory rates, shorter inspiratory times and surfactant are known to reduce the incidence. Pulmonary interstitial emphysema presents as a slow deterioration of the infant during ventilation. Pneumothorax is usually associated with sudden deterioration. The diagnosis of a tension pneumothorax is clinical and emergency management should not be delayed for a confirmatory X-ray. A ventilatory strategy allowing for permissive hypercapnia with lowest possible pressures, shorter inspiratory times and higher ventilatory rates may aid in the management of pulmonary air leaks. High frequency ventilation may help when conventional ventilation fails. Sedation and paralysis may be helpful when the infant fails to synchronize with the ventilator. Pulmonary air leaks are associated with increased mortality and morbidity and a higher incidence of intraventricular haemorrhages.     

Age-associated alterations of lipofuscin, membrane-bound ATPases and intracellular calcium in cortex, striatum and hippocampus of rat brain: protective role of glutathione monoester

Brain aging has become an area of intense research and a subject of much speculation fueled largely from the widely recognized fact that age is the biggest risk factor in most neurodegenerative diseases and age-related increase of reactive oxygen species is particularly detrimental to postmitotic tissues. In the present study, we have evaluated the possible role of glutathione monoester (GME), when administered intraperitoneally (12mg/kg body weight) for 20 days on age-associated changes in the levels of lipofuscin, Na+K+, Mg2+, Ca2+ ATPase activities and intracellular calcium levels in discrete brain regions of young and aged male albino Wistar rats. An age-associated increase in lipofuscin, intracellular calcium in cortex, striatum and hippocampus was observed and contradictorily, a decrease in the activities of membrane-bound enzyme activities was also observed. Supplementation of GME brought these changes to near normalcy. Thus, GME improves neuronal antioxidant status, thereby effectively attenuating any putative increase in oxidative stress with age.