Out of hospital point of care ultrasound: current use models and future directions.

INTRODUCTION: Ultrasound has evolved from a modality that was once exclusively reserved to certain specialities of its current state, in which its portability and durability lend to its broadly increasing applications. OBJECTIVES: This review describes portable ultrasound in the hospital setting and its comparison to gold standard imaging modalities. Also, this review summarizes current literature describing portable ultrasound use in prehospital, austere and remote environments, highlighting successes and barriers to use in these environments. DISCUSSION: Prehospital ultrasound has the ability to increase diagnostic ability and allow for therapeutic intervention in the field. In austere environments, ultrasound may be the only available imaging modality and thus can guide diagnosis, therapeutics and determine which patients may need emergent transfer to a healthcare facility. The most cutting edge applications of portable ultrasound employ telemedicine to obtain and transmit ultrasound images. This technology and ability to transmit images via satellite and cellular transmission can allow for even novice users to obtain interpretable images in austere environments. Portable ultrasound uses have steadily grown and will continue to do so with the introduction of more portable and durable technologies. As applications continue to grow, certain technologic considerations and future directions are explored.

Surveillance of drug-resistant tuberculosis in the state of Gujarat, India.

BACKGROUND: Limited information about the prevalence of drug-resistant tuberculosis (TB) has been reported from India, the country with the world's highest burden of TB. We conducted a representative state-wide survey in the state of Gujarat (2005 population: 56 million). METHODS: Mycobacterium tuberculosis isolates from a representative sample of new and previously treated smear-positive pulmonary TB (PTB) cases were subjected to drug susceptibility testing (DST) against first-line drugs at a World Health Organization supranational reference laboratory. Isolates found to have at least both isoniazid (INH) and rifampicin (RMP) resistance (i.e., multidrug-resistant TB [MDR-TB]) were subjected to second-line DST. RESULTS: Of 1571 isolates from new patients, 1236 (78.7%) were susceptible to all first-line drugs, 173 (11%) had any INH resistance and MDR-TB was found in 37 (2.4%, 95%CI 1.6-3.1). Of 1047 isolates from previously treated patients, 564 (54%) were susceptible to all first-line drugs, 387 (37%) had any INH resistance and MDR-TB was found in 182 (17.4%, 95%CI 15.0-19.7%). Among 216 MDR-TB isolates, 52 (24%) were ofloxacin (OFX) resistant; seven cases of extensively drug-resistant TB (XDR-TB) were found, all of whom were previously treated cases. CONCLUSION: MDR-TB prevalence remains low among new TB patients in Gujarat, but is more common among previously treated patients. Among MDR-TB isolates, the alarmingly high prevalence of OFX resistance may threaten the success of the expanding efforts to treat and control MDR-TB.

Conservative management of idiopathic clubfoot: Kite versus Ponseti method.

PURPOSE: To compare the long-term results of the Kite and Ponseti methods of manipulation and casting for clubfoot. METHODS: 42 patients (with 64 idiopathic clubfeet) were equally randomised to Kite or Ponseti treatments in the early weeks of life. 14 males and 7 females (34 clubfeet) were treated by the Kite method, whereas 13 males and 8 females (30 clubfeet) were treated by the Ponseti method. All the clubfeet were manipulated, casted, and followed up (for a mean of 3 years) by one experienced orthopaedic surgeon. The final results were compared. RESULTS: The success rates for the Kite and Ponseti treatments were similar (79% vs 87%). With the Ponseti method, the number of casts was significantly fewer (7 vs 10); the duration of casting required to achieve full correction was significantly shorter (10 vs 13 weeks); the maximum ankle dorsiflexion achieved was significantly greater (12 vs 6 degrees); and the incidence of residual deformity and recurrence was slightly lower. CONCLUSION: The Ponseti method can achieve more rapid correction and ankle dorsiflexion with fewer casts, without weakening the Achilles tendon.

When is a door not a door? The difference between documented and actual arrival times in the emergency department.

OBJECTIVES: An observational study to determine the difference between documented ambulance arrival times and the actual arrival times of patients from the ambulance into the emergency department. METHODS: In a busy, purpose built, modern emergency department with easy access, we recorded the time that ambulance borne patients were wheeled over the threshold of the clinical area and compared this to the times recorded by the ambulance trusts as the official ambulance arrival times. RESULTS: 352 ambulance arrivals were observed. Data were incomplete in 34 instances (9.5%) and were not included in the analysis. For the remaining 318 arrivals, the median time difference was 2 min 1 s (range 5 s to 21 min 45 s). In a subgroup of chest pain patients (45 patients), the median time difference was 2 min 11 s (range 23 s to 5 min 38 s). The difference between the chest pain group and the remaining patients was not significant (p = 0.528). CONCLUSIONS: There is inevitably some delay between the arrival of an ambulance and the arrival of the patient into a clinical area. This study quantifies that difference. In an era of stringent time related standards, this paper highlights the need for accurate recording of times to enable us to carry out valid audit of these standards. This study supports the redefining of an arrival time as the time when the patient arrives in the clinical area.

Conservative management of pulmonary lymphangioleiomyomatosis and tuberous sclerosis complicated by renal angiomyolipomas in pregnancy.

Both pulmonary lymphangioleiomyomatosis and tuberous sclerosis are rare diseases. The optimal management in pregnancy is unclear. A primigravida with pulmonary lymphangioleiomyomatosis and tuberous sclerosis complicated by worsening renal function secondary to angiomyolipomas was managed conservatively. Favorable maternal and neonatal outcomes were achieved. Pulmonary lymphangioleiomyomatosis is a consideration in tuberous sclerosis patients with respiratory symptoms. Tuberous sclerosis patients with pulmonary lymphangioleiomyomatosis require cautious and calculated expectant management in an effort to avoid adverse outcomes.

Genetic locus heterogeneity in Lafora's progressive myoclonus epilepsy.

In 1995, we mapped a gene for Lafora's progressive myoclonus epilepsy in chromosome 6q23-25. In 1997 and 1998, we reduced the size of the locus to 300 kb, and an international collaboration identified mutations in the protein tyrosine phosphatase gene. Here, we examine for heterogeneity through the admixture test in 22 families and estimate the proportion of linked families to be 75 to 85%. Extremely low posterior probabilities of linkage (Wi), exclusionary LOD scores, and haplotypes identify 4 families unlikely to be linked to chromosome 6q24.

Conjunctival transplantation for corneal surface reconstruction--case reports and review of literature.

Corneal persistent epithelial defects (PED) can occur due to various causes. In diffuse ocular surface disease, they often occur secondary to depletion of limbal stem cells. A number of complications occur secondary to PED and successful treatment usually requires conjunctival surgeries for corneal surface reconstruction. We report two cases of chemical injury successfully treated by two such procedures. This report highlights the encouraging results of limbal transplantation and reviews the literature in the management of PED with limbal stem cell loss.

Vanadate action on renal phosphate transport.

Insulin stimulates reabsorption of phosphate (Pi) in the renal proximal tubule. Previous studies have shown that vanadate can mimic the action of insulin on various tissues. In the present study, we tested the action of vanadate on renal Pi transport both in control rats and in rats made diabetic by injection of streptozotocin. Vanadate was administered orally for 4 days by inclusion in drinking water (0.7 mg/ml). By the 4th day, vanadate treatment of control rats did not change acid-base status, plasma glucose or the filtered load of Pi, but the urinary excretion of Pi was reduced to 2.5 +/- 0.9 compared with 17.6 +/- 3.5 mumol/mg creatine (P < 0.02) in untreated control rats. However, Na+/Pi cotransport by isolated brush border membrane vesicles was not different between the two groups. Findings in parathyroidectomized rats were similar. By the 4th day of vanadate treatment of diabetic rats, there was reversal of polyuria, polydipsia and hyperglycemia with no change in acid-base status. The filtered load of Pi was decreased by vanadate, and urinary Pi excretion also tended to decrease but not significantly. The values for Pi excretion were 21.4 +/- 7.6 in vanadate treated diabetics and 36.1 +/- 4.5 mumol/mg creatinine in untreated diabetics. In contrast to vanadate, daily injections of insulin did not change the filtered load of Pi but reduced urinary Pi excretion in diabetic rats to 15.6 +/- 2.2 mumol/mg creatinine (P < 0.02). These findings suggest that vanadate stimulated tubular Pi reabsorption in control rats but not in diabetic rats. Vanadate treatment of diabetic rats may tend to decrease tubular Pi reabsorption in contrast to the action of insulin.

Cytoskeletal modifications induced by organotin compounds in human neutrophils.

The polymerization of actin, a basic component of the cystoskeleton, was evaluated in human neutrophils after treatment with tributyltin (TBT), trimethyltin (TMT), triphenyltin (TPT), triethyltin (TET) or SnCl(2) for 2-30 min at 37 degrees C. TBT and TPT decreased the content of the polymerized form (F-actin) in resting neutrophils at all the times studied; in addition, after TBT and TPT treatment the response of the cells to a polymerizing stimulus (chemotactic peptide) was no longer detectable. These effects were observed under conditions where a cytotoxicity marker such as lactate dehydrogenase leakage remained unaffected. These results may explain the observed inhibition by TBT and TPT of basic cellular functions involving cell shape and motility, which are regulated by the cytoskeleton.

Abbott's fluorescence polarization immunoassay for cyclosporine and metabolites compared with the Sandoz "Sandimmune" RIA.

A new procedure for measuring cyclosporine in plasma has been introduced by Abbott Laboratories, involving their TDx instrumentation and fluorescence polarization immunoassay. Radioimmunoassay (RIA) and high-performance liquid chromatography are currently the conventional methods for measuring cyclosporine in plasma and whole blood. In an effort to find a method that will decrease the radioactive hazard, the reagent and supply cost, and the labor requirements associated with RIA procedures, we used specimens from transplantation patients to compare the Abbott assay with the Sandoz Sandimmune assay. We believe that the Abbott assay offers some advantages over the Sandimmune RIA procedure, providing a reliable but simpler and less hazardous technology.

Regulation of bile acid synthesis. Isolation and characterization of microsomal phosphatases.

In preliminary experiments, we have shown that rat liver microsomes possess phosphatase activity which was inhibited in the presence of sodium fluoride. We have now separated six microsomal phosphatase fractions appearing to be isoenzymes. They all possess different kinetic constants and are not equally inhibited by tartrate and fluoride ions, inhibitors of phosphatase activity. One phosphatase fraction, in fact, is almost completely unaffected by fluoride ion. More pertinent to our interest, these isoenzymes exhibit differing abilities to modulate the activities of hydroxymethylglutaryl CoA reductase, acyl-CoA:cholesterol O-acetyltransferase, and cholesterol 7 alpha-hydroxylase. Interaction of four of the fractions with rat liver microsomes resulted in a decrease in cholesterol 7 alpha-hydroxylase activity; two were without effect.

Biopharmaceutical aspects of FK-506.

FK is a potent immunosuppressive agent. FK can be analyzed in biologic fluids by EIA. The oral absorption of FK is rapid but variable in dogs. After intramuscular administration, FK is slowly and continuously absorbed. FK is primarily eliminated by metabolism. Less than 1% of the administered dose is excreted in the bile or the urine. After chronic intramuscular administration FK inhibits drug metabolism. Monitoring of FK levels in plasma is essential for the proper interpretation of efficacy and toxicity studies.

Cyclosporin A-induced cholestasis. The mechanism in a rat model.

Cyclosporin A (CyA) causes cholestasis in a significant proportion of transplant patients. Doses of 5, 10, and 15 mg CyA/kg body wt or the Miglyol 812 vehicle were administered intraperitoneally for 1, 2, and 3 wk to separate groups of rats to investigate the mechanism of this cholestasis. At 1 wk a dose-response relationship between serum CyA levels and increasing CyA doses was noted. A maximum CyA blood level was achieved by 2 wk with the 10- and 15-mg/kg doses. Subsequent studies were performed using the smaller (10 mg/kg) dose administered for 3 wk. This dose resulted in a marked increase in serum bile acid levels compared with vehicle-treated controls (24.6 +/- 4.0 vs. 4.3 +/- 1.2 mumol/L, p less than 0.001) without inducing significant changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, bilirubin, alkaline phosphatase, and albumin levels or hepatic architectural alterations. With CyA treatment, baseline bile flow decreased by 35% and bile salt secretion decreased by 25% compared with vehicle-treated animals. Cyclosporin A and vehicle-treated rats were infused intravenously with taurocholate (4 mumol/min X kg) for 2 h and then depleted of bile salts over the next 24 h. Bile samples collected over this period were graphed as bile salt secretion versus bile flow. The mean slope of the linear regression for the CyA-treated rats was 62% of the control, demonstrating a decrease in bile salt-dependent flow. Extrapolation of the linear regression to the ordinate demonstrated a 22% decrease in bile-independent flow with CyA treatment. Therefore, in our experimental model of CyA-induced cholestasis, the decrease in flow observed was the result of a decrease in both bile salt-dependent and bile salt-independent flows and occurred in the absence of significant biochemical or histologically evident hepatotoxicity.

Cyclosporine kinetics in healthy volunteers.

The pharmacokinetics of cyclosporine was studied in five healthy male volunteers following intravenous administration. The subjects received 2.1 mg/kg of cyclosporine as a two-hour intravenous infusion. Blood samples were collected over the subsequent 48 hours. Cyclosporine was extracted from whole blood and analyzed by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Following the intravenous infusion of cyclosporine, the drug exhibited multicompartmental behavior. The harmonic mean distribution half-life based on HPLC data was 0.45 hours, and the harmonic mean terminal disposition half-life was 6.2 hours. The clearance of cyclosporine based on HPLC cyclosporine concentrations was 3.9 mL/min/kg, and the volume of distribution at steady state of cyclosporine was 1.23 L/kg. Cyclosporine has a shorter half-life, lower clearance, and smaller Vss in healthy persons as compared to patient populations. The differences observed in the pharmacokinetics of cyclosporine in healthy persons as compared to patient populations may be due to differences in hematocrit, lipoprotein profiles, and/or concurrent drug therapy between the groups. Cyclosporine concentrations determined by RIA were consistently higher than those determined by HPLC, resulting in a significantly higher area under the blood concentration versus time curve and lower clearance rate for cyclosporine. We conclude that: (1) kinetic parameter estimates for cyclosporine are different in healthy individuals as compared with organ-transplant recipients, and (2) the kinetic parameters for cyclosporine are different, depending on the assay technique used.