Hemodynamic dysfunction in obesity hypoventilation syndrome and the effects of treatment with surgically induced weight loss.

Obesity hypoventilation syndrome (OHS), defined as a PaO2 less than or equal to 55 mmHg and/or PaCo2 greater than or equal to 47 mmHg, was found in approximately 8% of morbidly obese patients undergoing gastric surgery for morbid obesity and was frequently associated with clinically significant pulmonary hypertension and cardiac dysfunction. Forty-six morbidly obese patients, 26 with and 20 without OHS, underwent preoperative pulmonary artery catheterization. Although the two groups had similar values for percent ideal body weight, blood pressure, and cardiac index, the OHS patients had significantly higher mean pulmonary artery pressures (PAP), p less than 0.0001, and pulmonary artery occlusion pressures (PAOP), p less than 0.01. Eighteen OHS patients were restudied 3-9 months after gastric surgery. PaO2 increased from 50 +/- 10 to 69 +/- 14 mmHg, p less than 0.0001, and PaCO2 decreased from 52 +/- 7 to 42 +/- 4 mmHg, p less than 0.0001), after the loss of 42 +/- 19% excess weight. These changes were associated with significant decreases in PAP (from 36 +/- 14 to 23 +/- 7 mmHg, p less than 0.0001) and PAOP (from 17 +/- 7 to 12 +/- 6 mmHg, p less than 0.01). Significant correlations were noted between PAP and PAOP (r = +0.8, p less than 0.0001) and PAP and PaO2 (r = -0.6, p less than 0.0001). Both left ventricular dysfunction, defined as a PAOP greater than or equal to 18 mmHg, as well as pulmonary artery vasoconstriction, defined as PAEDP greater than 5 mmHg above PAOP, contributed to pulmonary hypertension in OHS patients. In conclusion, weight loss after gastric surgery for morbid obesity significantly improved arterial blood gases and hemodynamic function in OHS patients.     

Response of lower esophageal contractility to changing concentrations of halothane or isoflurane: A multicenter study

A multiple-center study was performed to determine the relationship between lower esophageal contractility, clinical signs, and anesthetic concentration as expressed by minimum alveolar concentration (MAC). One hundred four American Society of Anesthesiologists Class I through III patients were exposed to isoflurane (with and without nitrous oxide) or halothane in concentrations of 0.5, 1.0, and 1.5 MAC. Heart rate and systolic blood pressure were continuously monitored. Both the amplitude and frequency of spontaneous and provoked lower esophageal contractions were measured in situ by using a 24-F probe equipped with provoking and measuring balloons. Combined results demonstrated statistically significant correlations (P<0.001) between lower esophageal contractility and MAC. Spontaneous lower esophageal contractions decreased from 1.10±0.12 (SEM) contractions per minute (0.5 MAC) to 0.42±0.05 (1 MAC) to 0.18±0.05 (1.5 MAC). Provoked lower esophageal contractility values decreased from 45±4 mm Hg (0.5 MAC) to 29±3 (1 MAC) to 19±2 (1.5 MAC). Heart rate changes did not correlate with MAC, and systolic blood pressure correlated in only one of three centers. Intracenter and intercenter analyses failed to demonstrate a significant relationship between lower esophageal contractility and heart rate or systolic blood pressure. No intracenter differences in either amplitude or frequency of lower esophageal contractions were observed, despite differences in volatile agents, induction techniques and agents, patient populations, and duration of anesthesia. Our studies indicate that lower esophageal contractility may be an indicator of anesthetic depth as reflected by MAC, but further studies are needed to quantify the effects of surgical stimulus, intravenous anesthetics, vasodilators, anticholinergics, calcium channel blockers, beta-adrenergic agonists, and the presence of a nasogastric tube.     

Pulse-generated runoff: a new method of determining calf vessel patency

A non-invasive method of determining calf vessel patency before femorodistal bypass has been developed. This pulse-generated runoff (PGR) system generates blood flow in patent calf arteries by means of a pulsatile cuff even if the existing Doppler signal is inaudible. PGR was compared with pre-operative arteriography in 95 ischaemic limbs and both were compared with the peripheral resistance measured at operation in 62 limbs. There was a highly significant correlation between the PGR and arteriogram scores (rs = 0.74, P less than 0.001) but PGR tended to detect more patent vessels than arteriography. The peripheral resistance correlated better with PGR than arteriography (rs = -0.71 and -0.54 respectively, P less than 0.001). PGR is a simple, non-invasive method of determining calf and foot vessel patency pre-operatively.     

L-Dopa-responsive Parkinson's syndrome in association with phenylketonuria: In vivo dopamine transporter and D2 receptor findings.

Reports of parkinsonism in phenylketonuria are exceedingly rare. We report on a patient who had received a delayed diagnosis of phenylketonuria as an infant and subsequently developed levodopa-responsive parkinsonism at the age of 33. Single-photon emission computed tomography (SPECT) using (123)I-FP-CIT ([(123))I]-2 beta-carbomethoxy-3beta-(-4-iodophenyl)-N-(3-fluoropropyl)-nortropane) used to measure dopamine transporter levels on two occasions, 7 and 9 years after the onset of neurological symptoms, were normal. Iodine-123-iodo-lisuride SPECT (IBZM) imaging, however, showed reduced caudate over putamen binding. This combination of imaging findings indicates a possible upregulation of postsynaptic D2 receptors in the context of intact presynaptic dopamine nerve terminal density.     

Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Intergenerational studies of human birthweight from the 1958 birth cohort. II. Do parents who were twins have babies as heavy as those born to singletons?

OBJECTIVE: To ascertain whether maternal twinning influences the previously described association between the birthweight of singleton mothers and their infants. DESIGN AND SUBJECTS: The association between the birthweight of singleton parents and their offspring and that between twin parents and their offspring was compared using data from the 23-year-old sample of the 1958 British national birth cohort. The numbers available for full comparison were 1027 female and 611 male singleton cohort members, and 26 female and 17 male twin cohort members and their first singleton livebirths. RESULTS: Of the mothers who had been twins, half had been of low birthweight, and overall their mean weight was 700 g less than that of their singleton counterparts. Nevertheless, the mean birthweight of babies of twin mothers was 133 g, and of twin fathers 94 g, greater than of babies of corresponding singletons. For female, but not male, parents this difference persisted after adjustment for confounding variables. CONCLUSIONS: We suggest two possible reasons for the difference between the weight of babies of twin and singleton mothers. Firstly, the growth of twins becomes retarded late in pregnancy, possibly after a period critical in determining long-term reproductive effects. Secondly, the twin survivors were of higher birthweight than the original twin cohort, whilst the singleton survivors were more representative of all singleton births, thus introducing a possible bias.     

Post-herpetic neuralgia and topical capsaicin

Topical 0.025% capsaicin was used to treat 33 patients with post-herpetic neuralgia (PHN). Thirty-nine percent of those entering the trial achieved at least a good result and 55% were improved or better. Fifty-six percent of the 23 patients completing the study had good or excellent pain relief after 4 weeks. Seventy-eight percent of the 23 noted at least some improvement in pain. Post-capsaicin burning was a common, untoward effect in most patients and in about one-third was so unbearable that the trial was terminated prematurely. This treatment appears to be a useful modality in PHN, particularly in the elderly in whom oral medications are often poorly tolerated; however, it does require supervision. A double-blind, controlled trial is now necessary.     

Validation of a modified one-step rebreathing technique for measuring exercise cardiac output

A modification of the Farhi one-step rebreathing technique (1) is described for determining submaximal exercise cardiac output (Q). Factors critical in the estimation of Q are initial rebreathing bag volume and constant bag volume during the maneuver. By substituting a high flow rate analyzer (500 ml.min-1) for the recommended low flow rate mass spectrometer (60 ml.min-1), adding a recirculation circuit from the outlet of the analyzer to an inlet at the base of the rebreathing bag, and reducing the length of sample tubing to the analyzer, we were able to recirculate the subject's expired gas and achieve no loss of bag volume. No statistically significant differences in estimate of cardiac output were noted between the mass spectrometer and LB-2 analyzer with recirculation circuit during submaximal cycling. Heart rate and oxygen uptake were highly correlated with cardiac output and agreed well with the literature, irrespective of the CO2 analyzer system used. A unique feature of our method is that the subject's tidal volume is measured prior to the maneuver and then used as the initial rebreathing bag volume. Varying the bag volume by +/- 0.2 L from the tidal volume had no significant effect on the estimate of cardiac output during exercise. Now quick, reliable, and noninvasive measurements of cardiac output are feasible in subjects--not only in the laboratory but also in the field where a mass spectrometer is not readily portable.     

Optimization of non-isotopic in situ hybridization on formalin-fixed, paraffin-embedded material using digoxigenin-labelled probes and transgenic tissues.

The sensitivity of non-isotopic in situ hybridization (NISH), particularly on formalin-fixed, paraffin-embedded (FFPE) clinical tissues, has been the subject of controversy. Generally, NISH has been regarded as being less sensitive than radiolabelled procedures, although some reports have contradicted this. Accordingly, tissues from mice which were transgenic for variable amounts of the human alpha-1-antitrypsin gene were used to optimize the NISH procedure and to estimate the sensitivity. This approach showed that prolonged incubation of slides in final substrate resulted in high sensitivity--about 13 kb of target DNA. However, this prolonged incubation crucially depended on achieving minimal non-specific background staining. Many factors affected the degree of background staining, but five were particularly important. First, the method of mounting cut sections onto slides. Second, the length of the probe (ideally less than 400 bp). Third, the procedure for proteolytic digestion. Fourth, the denaturation technique, and fifth, the quality of the dextran sulphate used in the hybridization mix. The optimized protocol showed variable patterns of mRNA distribution in the transgenic mouse livers, while DNA distribution appeared uniform.