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Biomedical subjects

J Stocks

Publications and source records attributed to J Stocks.

At least 55 records · Page 3Linked to original sources

Comparison of nitrogen washout and plethysmographic measurements of lung volume in healthy infants.

Functional residual capacity (FRC), the only lung volume to be assessed routinely in infants, can be measured using plethysmography or gas dilution. Although it is well recognized that both methods yield similar FRC values in healthy adults, gas dilution techniques have consistently produced lower values in healthy infants when compared with plethysmography. However, interpretation of this difference is difficult since data comparing the different techniques within the same infants have rarely been reported. We performed paired measurements of FRC using an automated open-circuit nitrogen washout technique (FRCN2) and whole-body plethysmography (FRCpleth) in 11 healthy infants with a median age of 12 months (range, 2 to 18 months). The mean (SD) FRC was 21.7 (4.0) ml/kg for the N2 washout and 25.6 (4.9) ml/kg for plethysmography. The mean within-subject difference between FRCN2 and FRCpleth was 3.9 (range, -0.3 to 7.2) ml/kg (p = 0.001). Both N2 washout and plethysmography yielded reproducible results, with the mean of the coefficients of variation (CV) being 3.6 and 3.9%, respectively. The results from these paired measurements support previously reported data from separate populations of infants which suggest that gas dilution techniques consistently yield smaller values for FRC than do those measured by plethysmography.

Female

Respiratory compliance in infants--a preliminary evaluation of the multiple interrupter technique.

Measurements of total respiratory system compliance (Crs) using the multiple occlusion technique (MOT) in spontaneously breathing infants can be difficult to interpret in the presence of an unstable end-expiratory level. Similarly, measurements using the passive flow volume technique (PFV) are invalidated if there is alinearity of the expiratory time constant (Trs), irrespective of respiratory effort. For possibly overcoming these problems, we assessed the feasibility of a technique using multiple interruptions of of a single expiration (MIT), obtaining several pairs of volume-pressure data, from one expiration, which relate to a single end-expiratory level. Crs was measured in 16 infants aged 0.5 to 20 months using the MOT, MIT, and PFV technique. The MOT and the MIT each failed in one (different) infant, both succeeding where the other failed. The PFV technique failed in five infants in whom no acceptable plateau of airway pressure during occlusion and no Trs could be obtained from a single breath. Failure to obtain a linear Trs was accompanied by failure of the MIT in only one infant. Individual differences between the MIT and the MOT were less than 9%. However, the PFV measurements varied from -16.3% and +25.7% of the values from MIT or MOT. The greatest differences between Crs values coincided with the greatest differences between volume intercepts of the extrapolated volume-pressure (MOT, MIT) and flow-volume (PFV) data. From this preliminary study, the MIT proved as successful as the MOT, requiring fewer occluded breaths to measure Crs. In infants with a rapid respiratory rate, the data from several expirations can be merged and analyzed as for the MOT.

Humans

Polymorphisms at the GLUT1 (HepG2) and GLUT4 (muscle/adipocyte) glucose transporter genes and non-insulin-dependent diabetes mellitus (NIDDM).

In order to determine the possible contribution of the GLUT1 (HepG2) glucose transporter gene to the inheritance of non-insulin-dependent diabetes mellitus (NIDDM), two restriction fragment length polymorphisms (RFLPs) and the related haplotypes at this locus were studied in 48 Italian diabetic patients and 58 normal subjects. Genotype frequencies for the XbaI polymorphism were significantly different between patients and controls (XbaI: chi 2 = 9.80, df = 2, P less than 0.0079). A significant difference was also found in the allele frequencies between NIDDM patients and controls (chi 2 = 9.39, df = 1, P less than 0.0022), whereas no differences were found for the StuI RFLP. No linkage disequilibrium was detected between the XbaI and StuI RFLPs in this sample. The analysis of the four haplotype frequencies (X1S1, X1S2, X2S1, X2S2) revealed a significant difference between diabetic patients and controls (chi 2 = 14.26, df = 3, P less than 0.002). By comparing single haplotype frequencies, a significant difference between the two groups was found for the X1S1 and X2S2 haplotypes. A two-allele RFLP at the GLUT4 (muscle/adipocyte) glucose transporter gene, detected with the restriction enzyme KpnI, was also examined; no differences were found between patients and controls for this RFLP. The finding of an association between polymorphic markers at the GLUT1 transporter and NIDDM suggests that this locus may contribute to the inherited susceptibility to the disease in this Italian population.

Adipose Tissue

Sib-pair analysis of adenosine deaminase locus in NIDDM.

Recently, linkage between the ADA gene locus and MODY, a subtype of NIDDM, has been reported. The possibility that the region of chromosome 20q containing the ADA locus also may play a role in susceptibility to NIDDM needs to be investigated. Therefore, we examined the linkage between the ADA locus and NIDDM in affected siblings of 50 European white diabetic pedigrees--21 Italian and 29 British. Departure from independent segregation of the disease and an Alu VpA polymorphism within the 5' flanking region of the ADA locus was tested in the affected sib-pairs with the APM statistical method. After DNA amplification by the PCR and PAGE, five alleles were identified in the ALU VpA tract at the ADA locus in the two populations. Allele frequencies did not differ significantly between the two populations (chi 2 = 2.426, P > 0.05 [NS]). Analysis of the 50 diabetic sib sets, and independently of the Italian and British groups of affected sib pairs, revealed no segregation distortion between the marker locus and NIDDM. We conclude that mutations within or around the ADA locus are unlikely to play a major role in the etiology of NIDDM.

Adenosine Deaminase

Lipoprotein lipase genotypes for a common premature termination codon mutation detected by PCR-mediated site-directed mutagenesis and restriction digestion.

We have developed a procedure for the determination of a common mutation in exon 9 of the human lipoprotein lipase (LPL) gene. The mutation is due to a C-G transversion which creates a premature termination codon (Ser447-Ter) and results in a truncated LPL molecule lacking the C-terminal dipeptide SER-GLY. The mutation can be detected by polymerase chain reaction (PCR) amplification of exon 9 using a modified 3' amplimer that produces a 140 bp product containing a site for the restriction enzyme Hinf-1 in the presence of the mutation (G allele). The G allele was in strong linkage disequilibrium with a Hind-III restriction fragment length polymorphism (RFLP) allele in intron 8. Genotype determinations for the mutation can be performed by PCR amplification of genomic DNA, digestion with Hinf-1, and analysis of the products by polyacrylamide gel electrophoresis. The allelic frequency of the Ser447-Ter mutation in normal male Caucasian controls was 0.11. The frequency of the mutation was lower in a group of subjects with primary hypertriglyceridemia compared to normolipidemic controls.

Adult

Genetic polymorphisms at the human liver/islet glucose transporter (GLUT2) gene locus in Caucasian and West Indian subjects with type 2 (non-insulin-dependent) diabetes mellitus.

The liver/islet glucose transporter (GLUT2) is mainly expressed in the hepatocytes of the liver and the beta-cells of the pancreatic islets and a defect in this transporter could lead to diabetic phenotypes, such as relative hypoinsulinaemia and reduced uptake and metabolism of glucose in the liver. DNA from unrelated individuals was digested with the restriction endonucleases Bgl-I and Taq-I followed by blotting and hybridisation with a 32P-labelled GLUT2 cDNA which revealed three restriction fragment length polymorphisms (RFLPs) (B1, T1 and T2) in both Caucasian and West Indian populations. Linkage analysis between these variant sites demonstrated that the alleles of these polymorphisms were in strong linkage disequilibrium. Disease association of genetic variants at the GLUT2 locus with type 2 diabetes was examined with these RFLPs in both Caucasian (n = 54) and West Indian (n = 46) populations with type 2 diabetes. There were no significant differences in the frequency of alleles, genotypes or haplotypes between diabetic patients and non-diabetic controls. However, there were significant differences in the allele frequencies of all these three polymorphisms between Caucasian and West Indian populations.

Aged

The effect of triclofos sodium sedation on respiratory rate, oxygen saturation, and heart rate in infants and young children.

Chloral hydrate is frequently used to sedate infants for lung function testing. While no effect on respiratory function has been demonstrated, a recent study has reported a fall in oxygen saturation (SaO2) following sedation in wheezy infants. This study was designed to assess the effects of the closely related but less gastrically irritant drug triclofos sodium on respiratory rate (RR), heart rate (HR), and SaO2 in infants without cardiopulmonary disease. Paired measurements using respiratory inductance plethysmography and pulse oximetry were obtained in 10 infants (4-19 months of age) during natural and sedated sleep. Following sedation with triclofos, mean RR rose by 1.9 breaths min-1 (95% confidence intervals [Cl] of the mean difference: 0.13-3.7 min-1). Mean heart rate rose by 5.5 beats min-1 (95% Cl: -0.9-11.9 min-1). Mean SaO2 fell by 0.68% (95% Cl -1.8-0.45%). None of these changes are considered to be of clinical importance, and only the change in RR reached statistical significance at the 5% level.

Procedural Sedation

Influence of sedation on the Hering-Breuer inflation reflex in healthy infants.

The airway occlusion technique for measuring passive respiratory mechanics in infants relies on an ability to evoke the Hering-Breuer inflation reflex (HBR). However, the persistence of this reflex beyond the early newborn period remains controversial. We have recently demonstrated that there is no change in the strength of this reflex during the first two months of life in healthy infants during natural sleep. Measurements beyond this immediate newborn period are difficult without sedation, but it is unclear whether sedation itself may influence this reflex. To investigate the influence of sedation, the HBR was measured in 66 healthy, full-term infants aged 4-8 weeks. Thirty-three infants were measured during natural sleep, and 33 after triclofos sodium sedation (75 mg.kg-1). The strength of the HBR was assessed from the change in expiratory time (TE) following brief end-inspiratory airway occlusion, as compared to TE during spontaneous breathing. The mean increase in TE following occlusion was 89.45% (SD, 29.8; range, 44-175) in infants sleeping naturally, and 92.42% (SD, 31.2; range, 34-179) in sedated infants. Using unpaired t tests, no statistically significant difference was found between groups (P = 0.7516). We conclude that the strength of the HBR in healthy infants is not influenced by sedation with triclofos sodium, in doses normally used for lung function testing.

Female

Insulin receptor gene polymorphisms in type 2 (non-insulin-dependent) diabetes mellitus.

The insulin receptor has been proposed as a candidate gene for the inherited defect in Type 2 (non-insulin-dependent) diabetes mellitus and we therefore studied three restriction fragment length polymorphic sites, two revealed with the enzyme Sst1 and one by Rsa1, using two insulin receptor cDNA probes in 131 Caucasian Type 2 diabetic patients and 94 control subjects. The frequency of the six alleles studied did not differ significantly between the two groups. However, one allele, a 6.2 kilobase Rsa1 fragment (R+), was found more frequently in those diabetic subjects (n = 48) with a positive family history of diabetes (R + frequency = 0.48) compared to those diabetic subjects (n = 63) with a negative family history (R + frequency = 0.34, p less than 0.05). These results suggest that this polymorphism may be a linkage marker for the genetic defect in a subgroup of Type 2 diabetic patients with a positive family history.

Aged

Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion.

Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal

Respiratory compliance during sedation, anesthesia, and paralysis in infants and young children.

Although total respiratory compliance (Crs) has been shown to fall in adults on induction of halothane anesthesia, no successful paired studies have been reported in children. The multiple occlusion technique was used to measure Crs in 17 infants and young children during sedated sleep (CrsS) and shortly after, following induction of halothane anesthesia (CrsA). Crs fell in all but one infant after induction of anesthesia, with a mean fall of 34.7% (range 0-58%). This was accompanied by a reduction in tidal volume and increase in frequency in every case. In 7 of the 17 children, who were to be paralyzed for surgical purposes, Crs was also measured in this anesthetized-paralyzed state. When tidal volume administered during manual ventilation was similar to that observed during measurement of CrsA, Crs during this low-volume ventilation was similar to CrsA. When tidal volume was increased and Crs remeasured, there was a significant increase in every case, with the high-volume Crs within 10% of CrsS in all but one child, in whom there was a 31.4% increase with respect to CrsS. Changes in tidal volume accounted for approximately 50% of the variability in each state. These results demonstrate a highly significant fall in Crs in infants and young children after induction of halothane anesthesia. In addition it appears that this reduction in Crs can be reversed by paralyzing the child and manually ventilating with tidal volumes approximating those seen during sedation.

Anesthesia

Persistence of the Hering-Breuer reflex beyond the neonatal period.

There is conflicting evidence regarding the persistence of the Hering-Breuer reflex (HBR) beyond the 1st wk of life. This study was designed to assess the influence of postnatal age on the HBR. The airway occlusion technique was used to assess changes in respiratory timing during stimulation of the HBR in healthy full-term unsedated infants measured shortly after birth and at 6-8 wk of life. The strength of the HBR was assessed from the relative change in expiratory time (TE) after end-inspiratory occlusion compared with resting TE during spontaneous breathing. Paired studies were performed in 31 infants at approximately 2 days and 6 wk of age. There was a significant increase in TE during each occlusion in every infant irrespective of age at measurement. No maturational changes were observed. The increase in TE after end-inspiratory occlusion was 91.9 +/- 31.6% (SD) (range 38-158%) at approximately 2 days and 89.8 +/- 30.7% (range 44-175%) at approximately 6 wk. We conclude that the activity of the HBR during tidal breathing persists beyond the neonatal period and that there is no statistically significant change in its strength during the first 2 mo life in healthy infants during natural sleep.

Aging