The human obesity gene map: the 2001 update

This report constitutes the eighth update of the human obesity gene map, incorporating published results up to the end of October 2001. Evidence from the rodent and human obesity cases caused by single-gene mutations, Mendelian disorders exhibiting obesity as a clinical feature, quantitative trait loci (QTLs) uncovered in human genome-wide scans and in crossbreeding experiments in various animal models, association and linkage studies with candidate genes and other markers is reviewed. The human cases of obesity related in some way to single-gene mutations in six different genes are incorporated. Twenty-five Mendelian disorders exhibiting obesity as one of their clinical manifestations have now been mapped. The number of different QTLs reported from animal models currently reaches 165. Attempts to relate DNA sequence variation in specific genes to obesity phenotypes continue to grow, with 174 studies reporting positive associations with 58 candidate genes. Finally, 59 loci have been linked to obesity indicators in genomic scans and other linkage study designs. The obesity gene map depicted in Figure 1 reveals that putative loci affecting obesity-related phenotypes can be found on all chromosomes except chromosome Y. A total of 54 new loci have been added to the map in the past 12 months, and the number of genes, markers, and chromosomal regions that have been associated or linked with human obesity phenotypes is now above 250. Likewise, the number of negative studies, which are only partially reviewed here, is also on the rise.     

Dobutamine and gastric-to-arterial carbon dioxide gap in severe sepsis without shock

OBJECTIVES: To evaluate the effect of an early dobutamine infusion on gastrointestinal perfusion in patients with severe sepsis. DESIGN: Prospective, randomized, controlled, multicenter clinical study. SETTING: Six medical and/or surgical intensive care units (ICU) of teaching hospitals. PATIENTS: Forty-two patients with severe sepsis. INTERVENTIONS: Patients were divided into two groups according to gastric-to-arterial CO2 gap (DeltaCO2) [normal DeltaCO2 group ( n=17): DeltaCO2 < or = 8 mmHg; increased DeltaCO2 group ( n=25): DeltaCO2 > 8 mmHg]. Patients within each group were then randomized to receive either dobutamine (5 microg/kg per min) or saline for 72 h. MEASUREMENTS AND MAIN RESULTS: SAPS II was similar in both groups [group 1: 44.0 (33.0-56.5); group 2: 48.5 (40.5-59.0), p=0.27]. At ICU admission, mean arterial pressure was lower in the high DeltaCO2 group [73.0 (67.0-79.5) mmHg, p=0.03] than in the normal DeltaCO2 group [84.0 (73.7-104.0) mmHg] while blood lactate [normal DeltaCO2 group: 1.6 (0.8-2.3); high DeltaCO2 group: 1.6 (1.1-1.9) mmol/l] was similar for the two groups. DeltaCO2 was significantly lower in the normal DeltaCO2 group [5.0 (2.0-6.0) mmHg)] than in the high DeltaCO2 group [11.0 (10.0-19.0) mmHg]. Dobutamine infusion did not significantly change hemodynamics, blood lactate concentration or tonometric parameters in any group within the first 72 h and had no particular beneficial effect in this population. CONCLUSIONS: An early infusion of dobutamine at a fixed dose of 5 microg/kg per min during the first 72 h of severe sepsis does not influence gastric DeltaCO2.     

Estrogenic activity and metabolism of n-butyl benzyl phthalate in vitro: identification of the active molecule(s)

Some phthalates are suspected to disrupt the endocrine system, especially by mimicking estrogens. N-butyl benzyl phthalate (BBP) has estrogenic effects in vitro but not in vivo. The aim of this study was to identify the active molecule(s) (parent compound and/or metabolite(s)) involved in the estrogenic activities of BBP. The estrogenic effects of BBP and its in vivo metabolites were assessed using the following tests: E-Screen, ER binding, and PR induction tests on the human breast cancer cell line MCF-7 (ER(+)). BBP, the parent compound, was a partial agonist. It stimulated MCF-7 proliferation in the E-Screen assay and increased cytosolic progesterone receptors (PR) levels in a concentration-dependent manner. No BBP metabolites were active except hippuric acid (HA), which had a weak effect at very high concentrations. BBP and HA stimulatory effects on MCF-7 proliferation were antagonized by tamoxifen. However, no competition was observed between BBP or HA and 17beta-estradiol for binding to the estrogen receptor (ER). BBP metabolism by MCF-7 cells was also investigated. After a 48-h incubation, only 10% of the initial BBP remained in the culture medium, demonstrating that BBP was extensively metabolized by the MCF-7 cells. The radioactivity recovered in the medium was represented by: mono-n-butyl phthalate (MBuP, 25%) and mono-n-benzyl phthalate (MBeP, 48%), phthalic acid (6%), and benzoic acid (3%). Since none of these metabolites had estrogenic activities, this study demonstrates that the parent compound was the active molecule involved in the in vitro estrogenic effects of BBP.     

Management of retrohepatic inferior vena cava injury during hepatectomy for neoplasms

The aim of this article is to discuss the management of retrohepatic inferior vena cava injury during hepatectomy for neoplasms. Step-by-step hepatic vascular exclusion, digital compression, finger pinching, and surface-to-surface suturing were used in the management of retrohepatic inferior vena cava injury during hepatic resection in 16 cases： 12 patients underwent exclusion of the hepatic artery and portal vein by portal triad clamping （PTC） only;     

A novel instrument for assessing the retinal red reflex for non‐ophthalmic health professionals

Background : The direct ophthalmoscope is the standard instrument for assessing retinal red reflexes when screening for cataract, however, it is expensive and often not available to non‐ophthalmic health professionals. The pen torch ophthalmoscope is a new economic alternative for this purpose. This study aimed to determine its accuracy in assessing retinal red reflexes and to compare it to the direct ophthalmoscope. It is anticipated that this instrument will be useful in detecting both congenital and adult type cataracts. Methods : Eighteen health professionals evaluated the retinal red reflexes of 68 subjects at the Dunedin Hospital Eye Clinic with both the direct ophthalmoscope and the pen torch ophthalmoscope. Three groups of seven, six and five observers assessed both eyes of 24, 21 and 23 subjects, respectively, resulting in 1,574 examinations. Results : Compared to the direct ophthalmoscope, the pen torch ophthalmoscope exhibited lower sensitivity (68 per cent versus 75 per cent), but higher specificity (72 per cent versus 63 per cent) and lower over‐referral (false positive) rates by nine per cent. The positive predictive value in respect to identifying for cataract was better for the pen torch ophthalmoscope (71 per cent) than for the direct ophthalmoscope (66 per cent), while the negative predictive value was slightly worse (70 per cent and 73 per cent, respectively). When compared to the direct ophthalmoscope, 15/18 observers felt the pen torch ophthalmoscope was accurate enough, one felt it was just as good and two did not respond. Conclusions : This pilot study demonstrates that the pen torch ophthalmoscope is comparable to the direct ophthalmoscope in detecting abnormal retinal red reflexes in adults with cataracts. At six per cent of the cost of a direct ophthalmoscope, it may appeal to non‐ophthalmic health professionals in developed and developing countries. It may also increase the frequency of screening for cataract in children and adults. Further development and study of this pen torch ophthalmoscope prototype is warranted.     

Tyrosinemia type III: diagnosis and ten-year follow-up

Tyrosinemia type III, caused by deficiency of 4-hydroxyphenylpyruvate dioxygenase, is a rare disorder of tyrosine catabolism. Primary 4-hydroxyphenylpyruvate dioxygenase deficiency has been described in only three patients. The biochemical phenotype shows hypertyrosinemia and elevated urinary excretion of 4-hydroxyphenyl derivatives. We report the clinical and biochemical findings and the results of long-term follow-up in a new patient with this disorder presenting with severe mental retardation and neurological abnormalities. The clinical phenotype is compared with those reported in the three previously described patients.     

Early detection of abnormalities in partial epilepsy using magnetic resonance

The incidence of brain abnormalities determined by magnetic resonance in 30 consecutive children presenting with intractable complex partial seizures is reported. Images were optimised to visualise the hippocampus and cortical grey matter. Abnormalities of the hippocampus or temporal lobe were seen in all 19 children with clinical features of temporal lobe epilepsy and in six of the seven children with clinically unlocalised epilepsy. By contrast, in the four children with a clinical diagnosis of extratemporal epilepsy, no temporal or hippocampal abnormalities were seen. Generalised cortical abnormalities of uncertain significance were found in a total of 14 children from all groups. The identification of focal brain abnormalities using optimised magnetic resonance imaging enables early non-invasive assessment of children with intractable seizure disorders and the identification of patients for whom epilepsy surgery may be appropriate. It may also lead to a better understanding of the structural basis of intractable epilepsy, and thereby contribute to early treatment decisions.     

Pathologic rupture of the spleen during induction with ATRA in a patient with acute promyelocytic leukemia

Pathological rupture of the spleen is a rare but well recognized complication in hematological malignancies. Early clinical recognition of this life-threatening complication is necessary for rapid intervention. Here, we report on the case of a 26-year-old woman with acute promyelocytic leukemia who presented rupture of the spleen on day +2 of treatment with ATRA plus idarrubicin. In patients with acute leukemia, the presence of a painful abdomen and a sudden drop in hemoglobin levels, should alert of a possible splenic rupture, even without additional symptoms. This would facilitate an early treatment intervention with no modification to the chemotherapy schedule.