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Biomedical subjects

H Porter

Publications and source records attributed to H Porter.

At least 19 recordsLinked to original sources

Laryngeal ultrasound to assess vocal fold paralysis in children.

The purpose of this study was to assess the practicality and validity of laryngeal ultrasound to establish vocal fold movement in children with suspected vocal fold palsy. Fifty-five consecutive patients (age range three days to 12 years) with suspected vocal fold palsy underwent both laryngoscopy and laryngeal ultrasound. Ultrasonographic findings correlated with endoscopic findings in 81.2 per cent of cases. This, however, rose to a concordance rate of 89.5 per cent in patients aged over 12 months. Laryngeal ultrasound is well-tolerated, safe and non-invasive and the authors feel that it is a useful adjunct to endoscopy in the diagnosis of vocal fold palsy.

Bronchoscopy↗

Effect of global hypoxia-ischaemia followed by 24 h of mild hypothermia on organ pathology and biochemistry in a newborn pig survival model.

BACKGROUND: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. METHOD: Thirty-eight newborn pigs were subjected to 45 min of global HI by ventilating them with approximately 6% O2. On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0 degrees C for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35 degrees C for 24 h before NT was resumed and the animals then survived a further 48 h. RESULTS: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6 HT vs. 9 NT) or intestinal injury (8 HT vs. 2 NT, p = 0.07) was not different in the two groups. More HT piglets developed lung injury, 10 HT and 3 NT. Plasma [Na], [K], [Ca] and [Mg] increased significantly after the HI insult as compared to baseline values. For the 24-hour period plasma [K] and [Ca] were significantly higher in the HT group, the mean area under the curve (AUC) being for [K] AUC(HT) 4.4 mmol/l vs. AUC(NT) 3.9 mmol/l, p = 0.04 and for [Ca] AUC(HT) 2.7 mmol/l vs. AUC(NT) 2.5 mmol/l, p = 0.01, respectively. Aspartate aminotransferase peaked at 48 h in the HT group and at 24 h in the NT group. Creatinine peaked at >72 h in the HT pigs and at 48 h in the NT pigs. White blood cells (WBC) peaked at 12 h for the HT pigs and at 6 h for the NT animals. AUC of the WBC during the cooling was significantly lower in the HT pig (AUC(HT) 11.1 vs. AUC(NT) 15.3 10(3)/mm3, p = 0.04). The HT pigs needed more glucose to maintain normal glucose during the last 12 h of HT. Also HT animals needed more oxygen during cooling to maintain PaO2. CONCLUSION: Twenty-four hours of mild HT did not reduce damage in any organ. There was a slight increase in lung damage in the HT group. None of the biochemical or pathological changes were of clinical significance. We conclude that mild HT for 24 h does not affect the organ systems adversely when compared to NT. Additional glucose and oxygen is needed during cooling to maintain normal values.

Adrenal Glands↗

Correlation of prenatal ultrasound diagnosis and pathologic findings in fetal brain abnormalities.

OBJECTIVE: To determine the degree of agreement between prenatal ultrasound diagnosis of brain abnormalities and subsequent pathologic findings. METHODS: Between August 1993 and August 1999 there were 62 cases where a fetus with a prenatal ultrasound diagnosis of a brain abnormality other than neural tube defects underwent autopsy at the Regional Department of Pediatric Pathology. The cerebral diagnosis at ultrasound was compared with the findings at autopsy in all cases. RESULTS: In 47 of 61 (77%) cases the same defects were seen on ultrasound and at autopsy. The most common disparity was with the Dandy-Walker malformation or variant, where only six of the 14 (43%) cases prenatally diagnosed with this condition showed the same abnormality at autopsy. When fetuses with the Dandy-Walker malformation or variant were excluded, the scan findings correlated with autopsy in 41 of 47 (87%). In the main group with discordant findings, five of the seven cases where termination of pregnancy was undertaken had other fetal anomalies on ultrasound examination which were confirmed at autopsy. In the sixth case there was autolysis of brain tissue which affected detailed autopsy. CONCLUSIONS: A very high level of agreement between prenatal ultrasound and autopsy findings was found for all abnormalities of the fetal brain, except for the Dandy-Walker malformation or variant. Potential discrepancy in findings between ultrasound and autopsy should be explained to patients who are considering termination of pregnancy for the Dandy-Walker type of abnormality.

Autopsy↗

Influence of mild hypothermia after hypoxia-ischemia on the pharmacokinetics of gentamicin in newborn pigs.

The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39 degrees C) for 72 h (n = 8) or mild hypothermia (35 degrees C) for 24 h followed by normothermia (39 degrees C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39 degrees C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.

Animals↗

The Opitz syndrome gene product, MID1, associates with microtubules.

Opitz syndrome (OS) is a genetically heterogeneous disorder characterized by defects of the ventral midline, including hypertelorism, cleft lip and palate, heart defects, and mental retardation. We recently identified the gene responsible for X-linked OS. The ubiquitously expressed gene product, MID1, is a member of the RING finger family. These proteins are characterized by an N-terminal tripartite protein-protein interaction domain and a conserved C terminus of unknown function. Unlike other RING finger proteins for which diverse cellular functions have been proposed, the function of MID1 is as yet undefined. By using the green fluorescent protein as a tag, we show here that MID1 is a microtubule-associated protein that influences microtubule dynamics in MID1-overexpressing cells. We confirm this observation by demonstrating a colocalization of MID1 and tubulin in subcellular fractions and the association of endogenous MID1 with microtubules after in vitro assembly. Furthermore, overexpressed MID1 proteins harboring mutations described in OS patients lack the capability to associate with microtubules, forming cytoplasmic clumps instead. These data give an idea of the possible molecular pathomechanism underlying the OS phenotype.

DNA Mutational Analysis↗

In vitro heating of human fetal vertebra by pulsed diagnostic ultrasound.

The temperature rise generated at the surface of unperfused human fetal vertebrae in vitro by an ultrasound beam with characteristics typical of those used in pulsed Doppler examinations has been measured. The bone samples were from fetuses that ranged in age from 14 to 39 weeks, dating from the last menstrual period. The samples were embedded in agar gel and the temperature rise at their surface was measured using a 50-microm diameter K-type thermocouple. The power in the ultrasound beam was 50 +/- 2 mW and the -6 dB diameter was 2.9 mm. The temperature rise at 295 s ranged from 0.6 degrees C in the youngest sample to 1.8 degrees C in the oldest. Approximately 70% of the temperature rise occurred in the first min.

Gestational Age↗

An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses.

Insulin-like growth factors (IGFs) and their receptors in the fetus are essential for growth and postnatal survival but the role of maternal IGFs is less well understood. Animal and in vitro evidence suggests that maternal IGF-I may have important effects on placental function. Recent work in humans suggests that although there is no relationship between maternal serum IGF-I and normal fetal growth, levels are low in pregnancies complicated by fetal growth restriction due to placental dysfunction. A prospective and observational study was undertaken of the distribution and concentration of placental type I IGF receptors (IGF-IR) in women with small for gestational age (n=26) or appropriately grown (n=14) fetuses. Women were scanned biweekly from 24 weeks to delivery and cases (birthweight <5th centile) were assigned to two groups: 'fetal growth restriction' (FGR; umbilical artery pulsatility index [UAPI] > +2 s.d.; n=16) and 'normal small for gestational age' (SGA; normal UAPI, growth velocity and amniotic fluid; n=10). Immunohistochemistry of the IGF-IR was performed on formol saline-fixed placental biopsies obtained at delivery. In control pregnancies IGF-IR were present in villous endothelium and stroma, trophoblast and decidua and their distribution and density were unchanged in both SGA and FGR pregnancies. We hypothesize that a therapeutic elevation of maternal IGF-I in FGR pregnancy might lead to enhanced placental function and so fetal growth. Our findings of normal localization and density of placental IGF-IR in FGR encourage us to extend our work to look at the effects of maternal IGF-I on the transport of glucose and amino acids.

Chorionic Villi↗

The importance of CD34+/CD33- cells in platelet engraftment after intensive therapy for cancer patients given peripheral blood stem cell rescue.

The study was designed to determine whether the number of CD34+/CD33- cells given at autologous peripheral blood stem cell (PBSC) rescue after intensive therapy for cancer was a better predictor of platelet engraftment than the total number of CD34+ cells infused. Comparison between the total number of CD34+ cells/kg infused with the number of CD34+/CD33- cells/kg infused showed that, generally, 2 x 10(6) total CD34+ cells contained 1.38 x 10(6) CD34+/CD33- cells. There was poor correlation between the number of CD34+/CD33- and CD34+/CD33+ cells in the graft (r = 0.332). Engraftment times for platelets and neutrophils were evaluated in 68 patients. There was no significant difference between the times for platelets to reach >25 x 10(9)/l or neutrophils to reach >0.5 x 10(9)/l among patients who received > or <2 x 10(6) total CD34+ cells or > or <1.38 x 10(6) CD34+/CD33- cells although the latter was consistently the better predictor. Platelet recovery to >50 x 10(9)/l and >100 x 10(9)/l was delayed significantly in patients who received <1.38 x 10(6) CD34+/CD33-/kg infused (P < 0.02 and P < 0.05, respectively). The number of CD34+/CD33- cells/kg infused was a stronger predictor of platelet recovery than the total number of CD34+ cells infused (P < 0.05 for platelets >50 or >100 x 10(9)/l). Although platelet recovery was delayed significantly in patients who had <4 x 10(4) granulocyte-macrophage colony-forming units (CFU-GM)/kg infused, the time delay between receipt of PBSCs and availability of the colony counts limits the use of this assay to patients who do not require stem cells to be given immediately. Our data suggest that the number of CD34+/CD33- cells given at PBSC rescue provide information about the quality of the graft necessary for long-term platelet engraftment. However, since the percentage of CD34+/CD33- cells shows considerable inter-patient variation, measurement of this cell population may be important in patients who experience poor stem cell mobilization or when a target dose of 2 x 10(6) total CD34+ cells/kg is not achieved.

Adolescent↗

Focal intestinal perforation in preterm infants is an emerging disease.

In order to elicit the pathogenesis of focal intestinal perforation in preterm infants we contrasted 8 infants who developed this disease with 16 gestation-matched controls. The cases were found to have lower birthweights for gestation (median standard deviation score of -1.02 in cases versus -0.08 in controls), and more frequently had pre-existing patent ductus arteriosus and intraventricular haemorrhage (88 and 63% in cases versus 25 and 6% in controls, respectively). There were similar rates of other perinatal variables in the two groups, including indomethacin and umbilical arterial catheter use. Conditions associated with fetal or neonatal hypoxia are important antecedents for this emerging distinct clinical entity.

Case-Control Studies↗

Trisomy 18: first-trimester nuchal translucency with pathological correlation.

Diagnosis of trisomy 18 was made following prenatal screening at 11 weeks' gestation for ultrasonographically detected nuchal translucency and subsequent chorionic villus sampling. An intact fetus was therapeutically aborted and pathological examination was undertaken. We conclude that, although the etiology of nuchal translucency remains unclear, it does not appear to be lymphatic or cardiac in origin.

Adult↗

Rapid and specific diagnosis of t(11;22) translocation in paediatric Ewing's sarcoma and primitive neuroectodermal tumours using RNA-PCR.

One case of paediatric Ewing's sarcoma and two peripheral primitive neuroectodermal tumours/extra-osseous Ewing's sarcoma were studied for the characteristic t(11;22) translocation, using a recently described RNA-polymerase chain reaction method (RNA-PCR). PCR products of the expected sizes were obtained from RNA derived from the Ewing's sarcoma and the peripheral primitive neuroectodermal tumours, but not from other paediatric malignancies. Direct sequencing of the RNA-PCR products confirmed the presence of the EWS-FLI-1 fusion transcript. In one case the presence of the translocation was confirmed by cytogenetic analysis. These results highlight the potential use of PCR for the rapid demonstration of diagnostically important tumour specific chromosome rearrangements.

Adolescent↗

High-dose intravenous immunoglobulin in the treatment of demyelinating neuropathy associated with monoclonal gammopathy.

We treated 2 patients with IgM monoclonal paraproteinemic demyelinating peripheral neuropathy (PPN) with monthly intravenous human immunoglobulin. Both patients had a steadily progressive course in spite of steroid and other immunosuppressive therapy for 3 years before starting the immunoglobulin therapy. Both had a rapid clinical improvement noticeable 5 to 10 days after the 1st immunoglobulin infusion lasting on the average of 3 to 6 weeks. Retreatment caused improvement after each consecutive infusion. There were no significant adverse side effects. High-dose IV human immunoglobulin can be a useful therapy in the treatment of PPN and warrants a large-scale controlled therapeutic trial.

Aged↗