Role of non-invasive ventilation in difficult-to-wean children with acute neuromuscular disease.

Weaning from mechanical ventilation in children could be time-consuming and on many occasions, leads to reintubation with its associate complications. We report two children with acute neuromuscular disease, in whom bi-level positive airway pressure (BiPAP) as a mode of non-invasive ventilation was successfully used to wean the child from ventilators and prevented the need for tracheostomy. Despite the limited number of studies published in the literature suggesting BiPAP as a mode of weaning from mechanical ventilation, the technique when applied correctly seems to be safe and effective in weaning and avoiding tracheostomy.

Prevention of postoperative acute renal failure.

Postoperative acute renal failure (PO-ARF) is a serious complication resulting in a prolonged stay and high mortality. Patients may be at risk for this problem because of an underlying medical illness, nature of surgery, nephrotoxin exposure, or combinations of these factors. An increase in the intra abdominal pressure above 20-mm Hg is associated with an increase in the incidence of PO-ARF. Based on many clinical studies in high-risk surgical patients and patients undergoing renal transplantation, the only proven management strategies for prevention of PO-ARF are adequate volume expansion and avoidance of hypovolaemia. Drugs known to be nephrotoxic should be avoided or used with caution. Three main pharmacological agents namely mannitol, frusemide and dopamine have been extensively tried in the prevention of PO-ARF. Mannitol has proven of value only in the presence of adequate volume expansion in attenuating renal dysfunction in transplant patients. Frusemide converts oliguric renal failure to non-oliguric renal failure. The bulk of the data, including that from prospective studies indicate dopamine is only a diuretic. Fenoldopam, a dopamine analogue, has shown early promise in reports. Calcium channel blockers have not been shown to improve the outcome in renal transplantation or help in the prevention of contrast-induced nephropathy. Atrial natriuretic peptide has not been proven to be of benefit in established renal failure and its role in prevention has not been assessed.

A comparative study of telomerase activity in sputum, bronchial washing and biopsy specimens of lung cancer.

The potential of telomerase, the ribonucleoprotein enzyme, as a non-invasive screening marker was studied in pre-bronchoscopy sputum (S), bronchial washings (W) and bronchoscopic biopsy (B) samples from individuals under evaluation for lung cancer. Out of the 52 cases studied, 42 were clinically suspected primary lung cancer patients and 10 had pulmonary disorders but had no clinical evidence of lung cancer. Fifteen (39.5%) S samples, 24 (63.1%) W samples and 32 (84.2%) B samples, which were cytologically/histopathologically positive were also positive for telomerase activity. Interestingly, 16 (42%) S samples, 20 (52.6%) W samples and 20 (52.6%) B samples, initially reported cytologically/histopathologically negative, showed detectable telomerase activity. Lung cancer was finally confirmed in these cases by repeat cytology/histopathology. However, telomerase activity was detected in 31 (81.6%) S, 26 (68.4%) W and 33 (86.8%) B samples of suspected lung cancer patients. Telomerase activity was negative in S, W, and B of four of the suspected cases, which ultimately turned out to be negative for lung cancer. Cytopathology/histopathology alone (including repeat attempts) identified 15 (39.5%) cases of sputum, 24 (63.1%) cases of bronchial washings and 32 (84.2%) bronchoscopic biopsy samples. Out of 10 controls, low telomerase activity was detected in only one (10%) of the bronchial washings, which later turned out to be due to large number of inflammatory cells. Telomerase activity assay of sputum carried sensitivity, specificity and diagnostic accuracy of 81.6, 100 and 86.5%, respectively, while that for bronchial washing was 68.4, 100 and 76.9%, respectively, and for bronchoscopic biopsy samples was 86.8, 100 and 88.1%, respectively. A positive correlation (P<0.01) was seen between age and telomerase activity in sputum, bronchial washing and biopsy samples but no significant correlation was seen between sex and telomerase activity or duration of smoking and telomerase activity. A significant positive correlation was observed between staging and telomerase activity in sputum (P<0.01), bronchial washing (P<0.01) and biopsy samples (P<0.01). Our findings indicate that telomerase is a specific marker for malignant lung disease and can complement cytology/histopathology in the diagnosis of lung cancer. Sputum telomerase assay holds the potential for early and non-invasive diagnosis of lung cancer.

Vitamin C augments chemotherapeutic response of cervical carcinoma HeLa cells by stabilizing P53.

Human Papilloma Virus (HPV) is associated in most instances with cervical cancer. The HPV oncoproteins target P53 protein for degradation, leading to deregulation of cell cycle. We investigated whether stabilization of P53 in cervical cancer cells, by downregulating HPV transcription would restore the apoptotic ability of these cells. Our findings show that vitamin C downregulates the redox sensitive transcription factor AP-1 and decreases one of its transcription targets HPV E6, and stabilizes P53. This was associated with an increase in Bax and decrease in Bcl-2 and telomerase activity. Accumulation of P53 and its target gene bax then sensitized HeLa cells to cell-cycle arrest, cell death/apoptosis induced by cisplatin, and etoposide. Increasing drug sensitivity of cervical carcinoma cells by stabilizing P53 using vitamin C is a novel approach and has potential clinical relevance.

Telomerase-A molecular marker for cervical cancer screening.

Cervical cancer is one of the most common cancers in women and can be routinely screened for by the Papanicolaou smear. Screening for HPV high-risk types 16 and 18 has augmented the sensitivity of this test, but still some cases remain undetected. We have investigated the utility of assaying telomerase activity as a possible screening marker for cervical cancer. Telomerase activity was studied in relation to HPV 16/18 infection, Papanicolaou smear cytopathology, and biopsy histopathology in a total of 88 subjects, consisting of 29 cervical cancer cases, 19 control hysterectomy samples, 16 precancerous cervical scrapes, 6 cervical samples from other gynecological malignancies, and 18 normal healthy cervical scrapings. Telomerase activity was detected in 96.5% of cervical tumor samples and in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples and in cervical scrapings of normal healthy controls. Telomerase assay had a diagnostic accuracy of 95.8 in tissue samples, 79.1 in scrapings and 91.2 in all. Whereas HPV-16/18 subtyping had a diagnostic accuracy of 89.5% in tissue samples, 70.5% in scrapings, and 82.1% in all. There was also 71% agreement between telomerase activity and HPV-16/18 infection. The absence of telomerase activity in cervical scrapes from healthy women indicated the potential of telomerase to serve as a good screening marker for the early diagnosis of cervical cancer. For the first time we have also shown the ability of telomerase to detect micro and probably occult metastasis in gynecological malignancies.

Differential gene expression in apoptosis: identification of ribosomal protein S29 as an apoptotic inducer.

To identify genes that are specifically involved in apoptosis, poly(A)(+) RNAs were isolated from untreated control rat thymocytes and from adriamycin-induced apoptotic thymocytes. Directionally cloned cDNA libraries were then constructed in UNIZAP-XR vectors followed by biotin-based subtractive hybridization. Three clones were confirmed to be differentially expressed by dot blotting. Sequence analysis revealed homology to two genes previously identified, whereas one clone was novel and did not have homology to any known sequence. One clone was identical to the ribosomal protein S29, and the other was homologous to L8 ribosomal protein. Northern blot analysis revealed a marked increase in the expression of mRNA encoding ribosomal protein S29 in the apoptotic thymocytes compared to the controls. Transfection studies revealed that enhanced S29 expression resulted in increased apoptosis in rat thymocytes and HeLa cells as assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, TUNEL, FACS, and internucleosomal DNA fragmentation. This was accompanied by upregulation of p53, Caspase 3, and bax, whereas bcl-2 was downregulated as revealed by Western blotting. The current findings provide the first hint of a role for ribosomal protein S29 in the apoptotic process.

Chloroquine poisoning: report of two cases.

Two patients intentionally took chloroquine in overdose for different purposes. The first patient took chloroquine 2.7 g to terminate her pregnancy and the second patient took 3.75 g to terminate his life. The management of these two patients mainly consisted of gastric lavage, activated charcoal, ventilation, diazepam and inotropic support. The effect of chloroquine on the myocardium is discussed and the role of chloroquine as an abortifacient is reviewed. Hypokalemia should be recognized early and treated cautiously to avoid hyperkalemia. Refractory seizures not responding to benzodiazepine may require an antiepileptic drug.

Mutagenic and genotoxic effects of theophylline and theobromine in Salmonella assay and in vivo sister chromatid exchanges in bone marrow cells of mice.

The mutagenic and genotoxic effects of two methylxanthines, theophylline (TH) and theobromine (TB), were assessed in the Ames mutagenicity assay (in strains TA97a, TA100, TA102 and TA104) and in vivo sister chromatid exchanges (SCEs) in bone marrow cells of mice. These are the two most commonly used nervous system stimulators throughout the world. TH is used in the long-term treatment of asthma. Bacterial mutagenicity assay showed very weak mutagenic effects of both drugs in Salmonella strains TA102 and TA104 only in certain concentrations when S9 was added to it. No mutagenic effects were observed in any other strains used in this assay either with or without metabolic activation. But results of in vivo SCE assay indicate that these two drugs can induce significant SCE in bone marrow cells of mice.

New therapies for acute respiratory distress syndrome (ARDS):--a review.

Acute respiratory distress syndrome (ARDS) has been associated with high mortality. Improved understanding of the pathophysiology, recognition of precipitating events and improved management has decreased the mortality over the years. Mechanical ventilation is still the corner stone of the management of the disease. It is well recognised that high tidal volumes and airway pressures increase the morbidity, hence the need to use alternative modes of ventilation like pressure control with or without inverse ratio ventilation. Extracorporeal membrane oxygenation is still experimental and not easily available, whereas prone position to improve oxygenation is simple and inexpensive. The concept of pathological oxygen dependency and therapy aimed at supranormal values has failed to improve survival. Restricting the fluids to prevent further oedema formation in an already wet lung has improved the survival rate. Nitric oxide and surfactant have failed to produce desirable effect in large studies. Pharmacological support to inhibit inflammation with non steroidal anti-inflammatory drugs, antifungal agents, prostaglandin and corticosteroids have all failed. Interestingly corticosteroid rescue treatment in the late phase of ARDS has shown promise. Antiendotoxin and anticytokine studies which began with much enthusiasm is yet to produce desirable results.

Nasal midazolam and ketamine for paediatric sedation during computerised tomography.

We have studied the sedation achieved with a mixture of midazolam (0.56 mg/kg-1) and ketamine (5 mg/kg-1) administered nasally in 30 children weighing less than 16 kg undergoing computerised tomography. Assessment was two fold using a visual analogue scale; the radiologist/radiographer rated the exam from "failed examination" to "perfect working conditions" while the anesthetist's assessment ranged from "poor sedation" to "perfect sedation with clinical well being". This new method proved to be effective alone in 83% of the cases and there were no complications. The rapid onset obtained after intranasal midazolam and ketamine offers advantages over orally or rectally administered drugs. The absence of respiratory depression and oxygen desaturation suggests that this technique is safe and efficient in the CT room with its particular working conditions.

Accidental cannulation of the hepatic vein during pulmonary artery catheterisation--a case report.

A 22-year-old male was admitted to the adult ICU with a diagnosis of massive cardiomegaly and a large left ventricular thrombus, and needed Swan-Ganz catheterisation for proper haemodynamic monitoring. Insertion of the Swan-Ganz catheter resulted in hepatic vein cannulation. Pulmonary artery was successfully cannulated only when the patient was put in the head-up and right lateral position. It is suggested that to increase the success rate of patients with low cardiac output, cardiomegaly or pulmonary hypertension, they be placed in a head-up and right lateral position.

Controlled ventilation with Brain laryngeal mask.

A Brain laryngeal mask was assessed in fifty patients undergoing general anaesthesia who required controlled ventilation. The mask was inserted in all patients without any difficulty and the satisfactory seal obtained enabled ventilation in all patients in a wide range of positions. Airway obstruction occurred in seven patients secondary to downfolding of the epiglottis and this was rectified by reinsertion. The incidence of sore throat was 10%. The Brain laryngeal mask is a safe alternative to the tracheal tube for controlled ventilation during general anaesthesia.