UNLABELLED: Children with myelomeningocele are extremely short, yet little data exists on adult stature and anthropomorphic measurements. We measured the recumbent length, weight, arm length, sitting height and calculated body mass index of 54 adults with myelomeningocele. Mid parental height was also calculated. Measurements were compared with normative data. Patient charts were reviewed for history of hydrocephalus. The 27 males and 27 females had a mean age of 24.8 +/- 5.7 years. The mean length for adult females was 141.9 +/- 12 cm and was 152.1 +/- 13 cm for males. Patients with thoracic level of lesions were shorter than those with lumbar level who were, in turn, shorter than those with sacral levels. Recumbent length, sitting height, arm length and arm span were significantly smaller than expected values. Recumbent length was smaller than mid parental height. Those with ventriculoperitoneal shunts, required for hydrocephalus, were shorter than these without a shunt. CONCLUSION: Adults with myelomeningocele have significant short stature. Arm span is not an interchangeable measure with length for patients with myelomeningocele. Multiple factors are likely to be responsible for the observed short stature.

Adult↗

PubMed1995

Corneal virulence, cytopathic effect on human keratocytes and genetic characterization of Acanthamoeba.

Acanthamoeba keratitis is a sight-threatening complication of corneal trauma or contact lens wear. Although the majority of corneal isolates of Acanthamoeba belong to Group II in the Pussard-Pons classification based on cyst morphology, they have been placed in at least six species and their genetic relatedness is uncertain. The aim of this study was to determine the virulence of, and the relationship among, strains derived from the cornea, the nasal mucosa, and other environmental sources. To assess virulence, 10(4) trophozoites of each strain were incubated with monolayers of human corneal fibroblasts. By day 7, 12 of 29 strains tested had induced significant cytopathic changes. In addition, inocula of 10(4) cysts or trophozoites with 10(6) Corynebacterium xerosis were injected into the corneas of Porton rats; 11 amoebic strains induced infection within 7 days. The correlation between the virulence of trophozoites in vitro and in vivo was 86%. Using allozyme electrophoresis, 23 Acanthamoeba strains clustered into 5 major phylogenic divisions. Three divisions contained one or more strains that were virulent in the rat cornea. Virulent Pussard-Pons Group II strains clustered tightly to a fixed allelic difference of 13.6%. The eight corneal isolates clustered to 33%, dividing into three lineages. Five avirulent nasal isolates were strongly differentiated from other Group II strains. The results were not in accord with species designations based primarily on morphological criteria. These data suggest that particular subsets of Acanthamoeba strains are virulent in the human cornea.

Acanthamoeba↗

PubMed1995

MEG based brain laterality: sex differences in normal adults.

Magnetoencephalographic (MEG) auditory evoked fields produced by short tone pips were recorded from 34 normal adults (17 males, 17 females) and the 100 msec latency component (M100) localized in left and right hemispheres. Absolute M100 location in the antero-posterior dimension was calculated for each subject. M100 sources were significantly further anterior in the right hemisphere of males. Magnetic resonance (MR) based anatomy of the superior temporal gyri (STG) in a subset of 17 subjects showed that in the left STG of both males and females M100 sources were located approximately midway on the STG. In the right hemisphere of males, however, M100 sources were significantly further anterior on the STG than was the case for females. The findings are compatible with a sex based difference in right STG functional anatomy, with evidence of greater hemispheric lateralization in males compared to females based upon a predominantly right hemisphere contribution.

Adult↗

PubMed1995

Home monitoring of warfarin therapy in children with a whole blood prothrombin time monitor.

We prospectively evaluated a capillary whole blood prothrombin time (PT) monitor (Biotrack, Ciba Corning) in an outpatient pediatric anticoagulation clinic (40 clinic patients) and in age-matched healthy subjects (30 control subjects). Subsequently, 23 children requiring warfarin therapy were placed on a home program (home patients) using the PT monitor; their parents were trained and the results followed by clinic staff. The PT results were reported as internationalized normalized ratios (INRs). The laboratory and PT-monitor INR values were similar for the clinic patients and the control subjects (y = 0.76x + 0.38; r = 0.93; p < 0.001). The accuracy of the PT monitor (the difference between INR values and the laboratory INR) was best at an INR of 2.5 to 3.5; 90% of paired INR values were within 0.8 INR units. The average duration of monitoring for home patients was 13 months (range, 2 to 60 months). They had an average of 3 dose measurements (range, 1 to 11 measurements) and 1.8 dose changes (range, 0.6 to 4.5 changes) per month. Of the 599 measurements, 63% were within the therapeutic range, similar to those for clinic patients; the dose requirements were also similar. There was 1 significant bleeding event, a subdural hematoma in a patient with an INR of 4.1, and 1 catheter-related thrombotic event with an INR of 1.2; both children recovered. Of the 23 families, one discontinued home monitoring because of parental discomfort, 2 children died of their primary disease, 6 completed warfarin therapy, and 14 remain on the home program. We conclude that the whole blood PT/INR monitor is safe and offers practical advantages to children requiring anticoagulation.

Adolescent↗

PubMed1995

A cross-sectional study of catheter-related thrombosis in children receiving total parenteral nutrition at home.

We performed a cross-sectional evaluation of deep vein thrombosis (DVT) related to the use of central venous lines (CVLs) in all pediatric patients receiving home total parenteral nutrition at our institution (N = 12). All children (5 months to 17 years of age) were examined with bilateral upper limb venography. All CVLs were flushed daily with heparin (200 units). At the time of evaluation, 49 CVLs had been placed in the 12 children. Of the 39 CVLs removed, 27 (66%) were blocked; venograms had not been previously obtained except of one child. Eight children had clinical evidence of superficial collateral circulation in the upper portion of the chest and the upper extremities; five had intermittent symptoms of superior vena cava obstruction. On venography, 8 of the 12 children had extensive evidence of DVT; two were unilateral and six bilateral. Five children were treated with warfarin (0.12 to 0.28 mg/kg per day) to achieve an international normalized ratio of 1.4 to 1.8. Neither bleeding nor further CVL-related DVT has occurred. We conclude that the risk of CVL-related DVT in children requiring home total parenteral nutrition is high, and that venography should be performed early in the event of CVL blockage. A multicenter, controlled trial assessing optimal warfarin therapy in this patient population is indicated.

Adolescent↗

PubMed1995

High-dose folinic acid and 5-fluorouracil bolus and continuous infusion in advanced colorectal cancer: poor response rate in unselected patients.

We have conducted a retrospective study of high-dose folinic acid and 5-fluorouracil in 96 patients with advanced colorectal cancer. Patients received 200 mg m-2 (maximum 300-350 mg) folinic acid by infusion over 2 h followed by an i.v. bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 600 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for four cycles; thereafter patients with objective response continued to a maximum of eight cycles. The overall response rate was 10.6% in 85 evaluable patients. The median duration of response was 11 months. The median survival was 6 months. Toxicity was low, only one patient experiencing toxicity greater than WHO grade II (grade IV platelet toxicity). Diarrhoea, nausea, vomiting and mucositis also occurred but were mild and infrequent. Our low response rate may be related to factors such as patient characteristics or duration of treatment.

Adult↗

PubMed1995

Tropisetron alone or in combination with dexamethasone for the prevention and treatment of emesis induced by non-cisplatin chemotherapy: a randomized trial.

This study compared the efficacy and tolerability of tropisetron (Navoban, Novaban) alone or in combination with dexamethasone for the treatment of emesis induced by moderately emetogenic non-cisplatin chemotherapy. In total, 126 patients with cancer, who had never received chemotherapy and who required at least two courses of moderately emetogenic non-cisplatin chemotherapy each lasting for a minimum of 5 days, were recruited into the study. Patients were randomized to receive tropisetron, 5 mg o.d., plus either dexamethasone, 12 mg i.v. on day 1 followed by 4 mg orally b.i.d. on days 2-5, or placebo. Greater control of acute and delayed vomiting and nausea was achieved in patients given the tropisetron-dexamethasone combination than in those who received the tropisetron-placebo treatment. The majority of adverse events were mild and could be attributed to the chemotherapeutic regimen used or to the underlying disease. Patients and investigators both rated tropisetron alone or in combination with dexamethasone as a highly effective and well-tolerated antiemetic treatment. The results of this study show that tropisetron, 5 mg o.d., is an effective, well-tolerated and simple to use antiemetic treatment for patients receiving moderately emetogenic non-cisplatin chemotherapy. The addition of dexamethasone increases the efficacy of tropisetron without significantly decreasing its tolerability.

Antiemetics↗

PubMed1995

Oral and topical treatment of erectile dysfunction. Present and future.

A great deal of progress has been made in the pharmacological treatment of erectile dysfunction. At present, however, the most effective therapies require intracavernosal injections with a number of associated drawbacks. An increasing number of oral and transdermal agents have been introduced clinically or are at various phases in their development. It is evident that severe end-organ disease probably will not result in successful systemic therapy. Nevertheless, in men with intact or mildly dysfunctional erectile mechanisms, noninvasive treatments can offer some measure of success. Further study of individual and synergistic activity of available compounds is underway.

Administration, Oral↗

PubMed1995

[Intraoperative localization of metastases with a hand-held gamma probe].

A 50-y-old male patient with prostate cancer showed two suspicious lesions in bone scintigrams. They were assessed to be bone metastases by biopsy of the os ilium. After i.v. injection of 99mTc-HMDP a probe-guided localization permitted optimal surgical treatment. A bone metastasis in the os ilium was confirmed. The intraoperative detection with a hand-held gamma probe permitted accurate and complete excision of the tumour; the bone defect could thus be reduced to a minimum.

Bone Neoplasms↗

PubMed1995

Adverse effects of paternal opiate exposure on offspring development and sensitivity to morphine-induced analgesia.

We have shown previously that chronic morphine administration to adolescent male rats produced a number of gender specific deficits in their offspring. The purpose of the present studies was to extend our earlier observations by examining the acute, direct effects of morphine exposure to male rats on their fertility and the development of viable offspring. Sexually mature male rats were injected with a single dose of morphine (25 mg/kg) and 24 hr later were bred with drug-naive females. Fertility rates (vaginal plugs and pregnancies) were monitored throughout the breeding period as was the development of the offspring. Our results showed that a large, acute dose of morphine given to drug-naive male rats 24 hr before the initiation of breeding had no effect on fertility rates, but produced several adverse effects on fetal outcome. Litter sizes in morphine-derived offspring were considerably smaller than in controls and mortality rates were more than 6 times higher. Moreover, morphine-derived male, but not female, offspring had a significantly enhanced sensitivity to the antinociceptive effects of morphine. Collectively, these data suggest that acute paternal morphine exposure just before breeding with drug-naive females had no effect on fertility, but exerted negative effects on the viability and development of their offspring. These results represent the most compelling evidence to date that paternal opiate exposure can adversely affect fetal outcome and are particularly striking in that they were produced by a single injection of morphine. We are aware of no animal studies, clinical cases or anecdotal reports in humans in which such a phenomenon has been described.

Analgesia↗

PubMed1995

Green fluorescent protein as a reporter of gene expression and protein localization.

The green fluorescent protein (GFP) from the jellyfish Aequorea victoria is rapidly becoming an important reporter molecule for monitoring gene expression and protein localization in vivo, in situ and in real time. GFP emits bright green light (lambda max = 509 nm) when excited with UV or blue light (lambda max = 395 nm, minor peak at 470 nm). The fluorescence excitation and emission spectra of GFP are similar to those of fluorescein, and the conditions used to visualize this fluorophore are also suitable for GFP. Unlike other bioluminescent reporters, the chromophore in GFP is intrinsic to the primary structure of the protein, and GFP fluorescence does not require a substrate or cofactor. GFP fluorescence is stable, species-independent and can be monitored non-invasively in living cells and, in the case of transparent organisms, whole animals. Here we demonstrate GFP fluorescence in bacterial and mammalian cells and introduce our Living Colors line of GFP reporter vectors, GFP protein and anti-GFP antiserum. The reporter vectors for GFP include a promoterless GFP vector for monitoring the expression of cloned promoters/enhancers in mammalian cells and a series of six vectors for creating fusion protein to either the N or C terminus of GFP.

3T3 Cells↗

PubMed1994

Functional analysis of a transactivation domain in the thyroid hormone beta receptor.

Hormone-dependent transcriptional activation (AF-2) by the thyroid hormone beta receptor (TR beta) localizes to its carboxyl-terminal domain. A putative transactivation sequence within this domain was analyzed by mutating individual residues to alanine. Mutant receptor carboxyl-terminal domains were tested coupled to the heterologous DNA binding domain of Gal4. A single mutant receptor (E460A) showed normal hormone binding and activation, whereas several others (P453A, F455A, L456A, F459A) exhibited impaired transactivation which correlated with their reduced ligand binding. Two mutations (L454A, E457A) were able to dissociate these properties, generating transcriptionally defective mutant proteins with preserved hormone binding. A further conservative substitution (E457D) was also nonfunctional, and these three mutations were equally deleterious when tested in the context of full-length TR beta with a natural thyroid hormone response element containing promoter. This loss of activity was not due to altered DNA binding or expression of mutant receptors in cultured cells. They also retained the ability to recruit VP16-tagged retinoid X receptor in vivo as well as bind the basal transcription factors TFIIB and TBP in vitro. Our observations indicate that conserved hydrophobic (Leu454) and charged (Glu457) residues mediate AF-2 activity of TR beta, possibly via a co-activator that has yet to be identified.

Amino Acid Sequence↗

PubMed1994

Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura.

The most serious complication of childhood acute immune thrombocytopenic purpura (ITP), intracranial haemorrhage, occurs in about 1% of children with platelet counts below 20 x 10(9)/L. We conducted a randomised study to explore three treatment options in this high-risk group. 146 children (> 6 months and < 18 years old) with typical acute ITP and platelet counts of 20 x 10(9)/L or lower were randomised to receive high-dose intravenous immunoglobulin G (IVIgG) 1 g/kg on 2 consecutive days (n = 34), 0.8 g/kg once (n = 35), intravenous anti-D 25 micrograms/kg on 2 consecutive days (n = 38), or oral prednisone 4 mg/kg per day with tapering and discontinuation of prednisone by day 21 (n = 39). The rate of response as reflected by the number of days with platelet counts at 20 x 10(9)/L or lower and the time taken to achieve a platelet count 50 x 10(9)/L or more was significantly faster for both IVIgG groups than for the anti-D group (p < 0.05); the difference between prednisone and IVIgG was significant (p < 0.05) only for the IVIgG 0.8 g/kg group, and responses to the two IgG groups were similar. These differences in response rates were reflected in the percentages of children with platelet counts of 20 x 10(9)/L or lower at 72 hours following the start of treatment: 3% (IVIgG 0.8 g/kg x 1), 6% (IVIgG 1 g/kg x 2), 18% (anti-D), and 21% (oral prednisone 4 mg/kg/day). Treatment-associated toxicities included a fall in haemoglobin with anti-D (to less than 100 g/L in 24% of cases); weight gain with oral prednisone; and fever, nausea, vomiting, and headache with IVIgG. On the basis of these results, intravenous anti-D cannot be recommended as initial therapy for children with acute ITP and platelet counts of 20 x 10(9)/L or lower. A single dose of 0.8 g/kg IVIgG offers the fastest recovery for the least treatment; additional IgG or oral prednisone can be reserved for the one-third of children who continue to have platelet counts of 20 x 10(9)/L or less at 48-72 hours after the start of treatment.

Adolescent↗

PubMed1994

Laboratory model of lumbar disc protrusion: fissure and fragment.

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Cadaver↗