Intradermal transgenic expression of granulocyte-macrophage colony-stimulating factor induces neutrophilia, epidermal hyperplasia, Langerhans'' cell/macrophage accumulation, and dermal fibrosis

Bone age maturation and growth velocity were analyzed longitudinally by the TW2 RUS method standardized for Japanese children in 45 GH-treated boys with idiopathic GH deficiency (GHD). The patients were divided into three groups: Group I consisted of four isolated GHD patients who underwent spontaneous puberty without gonadotropin suppression treatment (GST) and had a mean final height of 151.9 cm; Group II consisted of 24 GHD patients with associated gonadotropin deficiency who received sex hormone replacement treatment (GRT) and had a mean final height of 165.3 cm; Group III consisted of 17 isolated GHD patients who underwent spontaneous puberty and had a mean final height of 158.3 cm after being treated with combined GH and GST. Bone age matured along with chronological age in Group I, whereas bone age in Group II decelerated significantly after a bone age of 12 years and did not reach a bone age of 14 years. Bone age maturation in Group III showed an intermediate pattern between Groups I and II; bone age decelerated significantly after a bone age of 12 years but mean bone age advanced beyond a bone age of 14 years. Height velocity in Group I during GH treatment decelerated rapidly after the pubertal growth spurt, as usually seen in normal puberty. A definite pubertal growth spurt was not observed in the height velocity of Group II during GH treatment before receiving GRT; the mean height velocity gradually declined, remaining at 3.5-4.5 cm/year even after 18 years. Mean height velocity in Group III during GH treatment and GST showed a similar tendency as Group II, but it declined more rapidly. Since a growth velocity of around 3 cm/year was preserved with GH treatment despite the decline in growth velocity, the slower the advance of bone age, the longer the treatment period and, therefore, the taller the final height achieved by GST compared to Group I. It is recommended to start GST at a bone age between 11.5 years and 13 years. The timing, namely when to start GRT in GHD with gonadotropin deficiency or when to stop GST in isolated GHD, can be estimated according to the patient's desired final height and bone age-growth potential.     

Time--frequency analysis of biosignals

The wavelet transform has a powerful time-frequency analysis and signal-coding tool suitable for use in the manipulation of complex nonstationary signals. This article provides an overview of the emerging role of wavelet-transform analysis in biomedical signal processing and analysis. It also provides a brief overview of the theory of the transform in its two distinct and very different forms: continuous and discrete. In conclusion, it has been shown that the wavelet transform is a flexible time-frequency decomposition tool that can form the basis of useful signal analysis, and coding schemes. It is envisaged that the future will see further application of the wavelet transform to biomedical signal analysis, as the emerging technologies based on them are honed for practical purposes.     

Crossover study of the haematological effects and pharmacokinetics of glycosylated and non-glycosylated G-CSF in healthy volunteers

A cross-over study of glycosylated and non-glycosylated G-CSF was performed in 20 healthy male volunteers to compare the effects of the different forms of G-CSF, the extent of inter-individual progenitor cell mobilization and to determine whether any differences observed were related to the serum concentrations of G-CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose of 5 microg/kg/d was significantly higher with the glycosylated than the non-glycosylated product (P = 0.02) as was the peak level of granulocyte-monocyte colony forming cells (GM-CFC) (P=0.03). The average GM-CFC count on days 5, 6 and 7 was 28% higher with the glycosylated product (P=0.003). Serum concentrations of G-CSF achieved were significantly higher with the non-glycosylated G-CSF, however, suggesting that the difference in bio-efficacy was not due to a difference in G-CSF stability. Marked inter-individual variation in progenitor mobilization was observed, but this was not related to serum G-CSF levels. The G-CSF concentrations on day 6 were approximately one third of those on day 1, with both forms of G-CSF.     

Urethral prolapse after collagen injection

A woman who was treated for intrinsic urethral sphincteric deficiency with periurethral injection of glutaraldehyde cross-linked collagen had prolapse of the urethral mucosa and recurrence of incontinence. She subsequently required surgical resection and a fascia lata sling. This is the first known occurrence of this postinjection complication.     

Finding coordinated atrial activity during ventricular fibrillationusing wavelet decomposition

Until recently, the ECG recorded during ventricular fibrillation was thought to represent disorganized and unstructured electrical activity of the heart. Using a new signal analysis technique based on wavelet decomposition, we have begun to reveal previously unreported structure within the ECG tracing. We report preliminary findings that provide the first evidence linking this structure to unexpected mechanical phenomena occurring in the heart     

Methimazole and propylthiouracil equally cross the perfused human term placental lobule

Propylthiouracil (PTU) is widely believed to cross the placenta less freely than methimazole (MMI) and is therefore regarded as the preferred drug for treatment of hyperthyroidism in pregnancy. Clinical studies comparing the two drugs show, however, no differences in maternal or fetal thyroid function. We investigated transfer from the maternal to the fetal circuit in the isolated perfused term human placental lobule of low and high doses of PTU (4 micrograms/mL and 40 micrograms/mL) and MMI (1.5 micrograms/mL and 15 micrograms/mL) in protein-free perfusate and low doses of both drugs with addition of 40 g/L of bovine albumin. Both drugs readily crossed the placenta, reaching equilibrium in all experiments in about 2 h. Drug concentrations in the two circuits fitted a two compartmental model. Transfer kinetics for the two drugs were similar, nonsaturable, and unaffected by addition of albumin. Clearances (mL.min-1.g-1, means +/- SD) of PTU from maternal to fetal circuits were: 0.229 +/- 0.110, 0.216 +/- 0.065, and 0.170 +/- 0.032; and for transfer of MMI: 0.165 +/- 0.025, 0.232 +/- 0.153, and 0.174 +/- 0.009 (for low doses without, low doses with, and high doses without albumin, respectively). Clearances of PTU from fetal to maternal circuits were: 0.147 +/- 0.072, 0.109 +/- 0.014, and 0.116 +/- 0.028; and for transfer of MMI: 0.095 +/- 0.029, 0.122 +/- 0.088, and 0.12 +/- 0.005 (in the same experiments). There was no significant difference between drugs or drug doses and no effect of addition of albumin. We conclude that PTU and MMI have similar placental transfer kinetics.     

Evaluation of biliary tract disease by ultrasonic B-mode scanning

To establish the value of diagnostic ultrasound (sonar) in the diagnosis of bilitary tract disease, 140 patients were scanned and also had a plain film of the biliary tract. Of these, 105 had contrast radiography and 123 were subjected to laparotomy. The results obtained suggest that in the absence of jaundice, sonar compares well with oral cholecystography in demonstrating the gallbladder, but is not as good as intravenous cholangiography in showing the duct system. In the presence of jaundice, however, sonar is considered the imaging investigation of choice.     

The effect of intravenous immunoglobulin on placental transfer of a platelet-specific antibody: anti-P1A1

The isolated perfused lobule of human placenta was used as an in-vitro model to study the effect of intravenous immunoglobulin (IVGG) on the placental transfer of a human platelet-specific antibody (anti-P1A1). Normal human IgG was shown to transfer from the maternal to the fetal circulation of the placental model after a lag period of 2-3 h. IVGG also transferred across the placenta but only after a longer lag period (3-4 h) than normal human IgG at the same concentration, which suggests that IVGG may contain a factor that inhibits the transfer of its own component IgG. The sensitive Western immunoblotting technique was used to demonstrate progressive transfer of anti-P1A1 antibody to the fetal circulation after a 2-3 h lag period. When IVGG and anti-P1A1 antibody were added simultaneously to the maternal circulation, the transfer of platelet-specific antibody was strongly inhibited by IVGG. The inhibitory effect of IVGG on anti-P1A1 antibody transfer was consistent for three different batches of the same IVGG product (Sandoglobulin). These studies provide the first scientific data to support the use of IVGG to inhibit antiplatelet antibody transfer as part of the antenatal management of neonatal alloimmune thrombocytopenia.     

A comparison between the life cycle cost of gravel and of bituminous surfacing options for feeder roads in Ghana

Feeder roads, which constitute a key component of rural transport infrastructure, play a vital role in rural development, but only 5% of the total feeder road network in Ghana has bituminous seal surfacing. The remaining 95% have either gravel or earth surfacing. However, gravel surfacing (G-S) is known to deteriorate rather rapidly necessitating expensive frequent maintenance while bituminous surfacing offers a more durable surfacing. Various life cycle cost studies have suggested that even though G-S may have lower initial construction costs, they tend to have higher life cycle costs than bituminous seal surfaced ones. However, since most of these studies are based on ideal maintenance practices, their conclusions do not reflect actual field conditions. This study seeks therefore to compare the life cycle cost of G-S with that of bituminous seal surfacing options for engineered feeder roads in Ghana using actual cost data. Data were collected from eight feeder road projects with G-S and a similar number with bituminous surfacing from six regions of Ghana completed between 2010 and 2013. The life cycle cost for each road was computed using a discount rate of 12% and an inflation rate of 15% over an analysis period of 21 years. The results for G-S are then compared with those for single bituminous seal surfacing and for double bituminous seal surfacing. The results are further compared with those from trial sections of an experimental study of Otta seal surfacing using natural gravel and using crushed rock as aggregates. The results suggest that based on the high initial construction costs of bituminous seal surfacing and actual low maintenance intervention practices, G-S remain the least cost option. The study recommends the need for alternative surfacing technology that does not involve bitumen.     

Substitution of Two Active‐Site Residues Alters C9‐Hydroxylation in a Class II Diterpene Synthase

Diterpenes form a vast and diverse class of natural products of both ecological and economic importance. Class II diterpene synthase (diTPS) enzymes control the committed biosynthetic reactions underlying diterpene chemical diversity. Homology modelling with site‐directed mutagenesis identified two active‐site residues in the horehound (Marrubium vulgare) class II diTPS peregrinol diphosphate synthase (MvCPS1); residue substitutions abolished the unique MvCPS1‐catalysed water‐capture reaction at C9 and redirected enzyme activity toward formation of an alternative product, halima‐5(10),13‐dienyl diphosphate. These findings contributed new insight into the steric interactions that govern diTPS‐catalysed regiospecific oxygenation reactions and highlight the feasibility of diTPS engineering to provide a broader spectrum of bioactive diterpene natural products.