Bone graft gel: autologous growth factors used with autograft bone for lumbar spine fusions

A method to combine autologous growth factors (AGF) with autologous bone graft in a bone graft gel for spine fusions is described. The bone graft gel can be inserted into cages for interbody fusions or used directly for posterolateral intertransverse fusions. Sixty patients have undergone spinal fusion surgery under this technique. No equipment problems have been encountered and no adverse effects observed that could be attributed to AGF. Early clinical outcomes indicated solid or maturing fusions in 58 of 60 patients. AGFs to enhance bone healing represent an economical and readily available autologous source of growth factors.     

Prevalence of drug resistance under the DOTS strategy in Hyderabad, South India, 2001-2003.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid (INH) and rifampicin (RMP), is considered a threat to TB control. Implementation of DOTS ensures high cure rates and prevents MDR. OBJECTIVE: To study the prevalence of MDR-TB from a retrospective analysis of the data in a tuberculosis unit where DOTS was implemented over a period of 6 years through public private mix (PPM). METHODS: Drug susceptibility testing of Mycobacterium tuberculosis samples isolated from the cultures of newly registered and retreatment sputum smear-positive cases during 2001-2003. RESULTS: During the study, 909 sputum-positive cases were registered and analysed. Of these, 714 were new and 195 were retreatment sputum-positive cases. INH resistance was found in 3.2% (23) of new and 9.2% (18) of retreatment cases. RMP resistance was present in 1.5% (11) of new and 7.2% (14) of retreatment cases. MDR was present only in 0.14% (1) of new and 2% (4) of retreatment cases. New cases had cure rates of 96% compared to 85% in retreatment cases. CONCLUSION: The prevalence of MDR-TB is low where success rates are high.     

Cardiopulmonary function of cats with respiratory distress induced by N-nitroso N-methylurethane

The purposes of this study were to determine the effects of positive end-expiratory pressure (PEEP) and end-expiratory lung volume on systemic blood flow, whether PEEP levels yielding maximum systemic oxygen transport are associated with maximum lung compliance, and the effects of end-expiratory lung volume on pulmonary resistance to gas flow, in an animal model of respiratory distress. Twelve cats were inoculated with 12 mg/kg N-Nitroso N-Methylurethane (NNNMU) to induce respiratory distress. The NNNMU caused a 76% decrease in disaturated phosphatidyl-choline of lung lavage, a 34% decrease in functional residual capacity (FRC), an 80% decrease in lung compliance, an 88% increase in pulmonary resistance to gas flow, a 43% decrease in PaO2, and a 37% decrease in oxygen consumption. Systemic blood flow and systemic oxygen transport were not significantly altered by the chemically induced respiratory distress. PEEP levels of 5.1 +/- 0.8 cm H2O returned end-expiratory lung volume to normal FRC levels. Increases in PEEP caused systemic blood flow to decrease even when end-expiratory lung volume was below or equal to normal FRC levels but did not significantly affect systemic oxygen transport, lung compliance, or pulmonary resistance. We conclude that in cats with NNNMU-induced respiratory distress: PEEP causes decreases in systemic blood flow, lung compliance and systemic oxygen transport are not clear indicators of optimal PEEP level, and returning end-expiratory lung volume to normal FRC does not significantly reduce pulmonary resistance to gas flow.     

Allosteric modulation of the muscarinic M4 receptor as an approach to treating schizophrenia

Current antipsychotics provide symptomatic relief for patients suffering from schizophrenia and related psychoses; however, their effectiveness is variable and many patients discontinue treatment due to side effects. Although the etiology of schizophrenia is still unclear, a leading hypothesis implicates an imbalanced dopaminergic system. Muscarinic acetylcholine (ACh) receptors regulate dopamine levels in key areas of the brain involved in psychosis, with the M(4) subtype emerging as a key regulator of dopaminergic hyperactivity. Unfortunately, no selective small molecule tools exist to provide pharmacological validation of this hypothesis. Here, we describe the discovery of a small molecule modulator, LY2033298, that is highly selective for human M(4) receptors by virtue of targeting an allosteric site on this receptor. Pharmacological assays confirmed the selectivity of LY2033298 for the M(4) receptor and revealed the highest degree of positive allosteric enhancement of ACh potency thus far identified. Radioligand binding assays also show this compound to directly potentiate agonist binding while having minimal effects on antagonist binding. Mutational analysis identified a key amino acid (D(432)) in the third extracellular loop of the human M(4) receptor to be critical for selectivity and agonist potentiation by LY2033298. Importantly, LY2033298 was active in animal models predictive of clinical antipsychotic drug efficacy indicating its potential use as a first-in-class, selective, allosteric muscarinic antipsychotic agent.