Maternal-fetal interactions and birth order influence insulin variable number of tandem repeats allele class associations with head size at birth and childhood weight gain

Polymorphism of the insulin gene (INS) variable number of tandem repeats (VNTR; class I or class III alleles) locus has been associated with adult diseases and with birth size. Therefore, this variant is a potential contributory factor to the reported fetal origins of adult disease. In the population-based Avon Longitudinal Study of Pregnancy and Childhood birth cohort, we have confirmed in the present study the association between the INS VNTR III/III genotype and larger head circumference at birth (odds ratio [OR] 1.92, 95% CI 1.23-3.07; P = 0.004) and identified an association with higher cord blood IGF-II levels (P = 0.05 to 0.0001). The genotype association with head circumference was influenced by maternal parity (birth order): the III/III OR for larger head circumference was stronger in second and subsequent pregnancies (OR 5.0, 95% CI 2.2-11.5; P = 0.00003) than in first pregnancies (1.2, 0.6-2.2; P = 0.8; interaction with birth order, P = 0.02). During childhood, the III/III genotype remained associated with larger head circumference (P = 0.004) and was also associated with greater BMI (P = 0.03), waist circumference (P = 0.03), and higher fasting insulin levels in girls (P = 0.02). In addition, there were interactions between INS VNTR genotype and early postnatal weight gain in determining childhood BMI (P = 0.001 for interaction), weight (P = 0.005), and waist circumference (P = 0.0005), such that in the approximately 25% of children (n = 286) with rapid early postnatal weight gain, class III genotype-negative children among this group gained weight more rapidly. Our results indicate that complex prenatal and postnatal gene-maternal/fetal interactions influence size at birth and childhood risk factors for adult disease.     

Pulmonary metastases from uterine malignancies: results of surgical resection in 133 patients

OBJECTIVE: The long-term results of the surgical treatment for patients with pulmonary metastases from uterine malignancies were clarified. METHODS: A total of 133 patients who underwent pulmonary metastasectomy for uterine malignancies were enrolled in the Metastatic Lung Tumor Study Group of Japan between March 1984 and February 2002. These patients constituted the study population, and their clinical, pathologic, and prognostic data were retrospectively analyzed. RESULTS: The morbidity and mortality rates related to the operation were minimal (1% and 1%, respectively). The 5- and 10-year survivals after the surgical resection in all cases were 54.6% and 44.9%, respectively. The 5-year survivals for each histologic type were estimated to be 46.8% for squamous cell carcinoma (n = 58), 40.3% for cervical adenocarcinoma (n = 13), 75.7% for endometrial adenocarcinoma (n = 23), 86.5% for choriocarcinoma (n = 16), and 37.9% for leiomyosarcoma (n = 11). In the univariate analysis, the following were shown to be associated with poor survival: primary tumor in the cervix, short disease-free interval (<12 months), large number of resected metastases (> or =4), and large tumor size (> or =3 cm). After mutual adjustment, short disease-free interval (<12 months) alone was related to risk of death (hazard ratio = 2.26, 95% confidence interval = 1.06-4.78) for 105 patients, excluding patients with choriocarcinoma and miscellaneous histologic types. CONCLUSION: Pulmonary metastasectomy for uterine malignancies is a safe and acceptable treatment to improve survival. Patients with a disease-free interval of 12 months or more are good candidates for this treatment if there is adequate control of the primary tumor without extrapulmonary metastasis.     

Activation of nuclear factor-kappa B and macrophage invasion in cyclosporin A-and tacrolimus-treated renal transplants

This retrospective study was designed to compare the efficacy of cyclosporin A (CyA) and tacrolimus (FK506) on chronic rejection (CR) associated with nuclear factor-kappa B (NF-kappaB) activation and macrophage invasion. Non-episodic day 50 protocol renal biopsy was performed in 63 consecutive patients with renal transplants from living donors, treated with either CyA or FK506. Southwestern histochemistry for NF-kappaB, immunostaining for CD68, and Banff classification were performed, and these findings were compared with outcome over 34 +/- 13 months. Compared with specimens from FK506-treated patients (n = 20), specimens from CyA-treated patients (n = 43) showed a significant increase in tubulointerstitial CD68-positive cells (1.5 +/- 0.9 vs. 0.9 +/- 0.8, p < 0.01), although no significant differences were observed in NF-kappaB activation. Specimens with Banff acute rejection (AR) grade > or = 1A (n = 20) showed increased macrophages (p < 0.01) compared with specimens with AR < 1A (n = 43). Specimens from patients with clinical AR prior to day 50 biopsy (n = 23) also showed increased macrophage invasion (p < 0.01) compared with specimens from patients without prior clinical AR (n = 40). The cumulative well-functioning (serum creatinine < 1.5 mg/dL) graft survival rate was significantly lower in patients with increased tubulointerstitial CD68-positive cells (n = 63, p < 0.05). Our findings suggest that tacrolimus is more effective than CyA against CR with respect to macrophage invasion and AR.     

Changes in body temperature during profound hypothermic cardiopulmonary bypass in adult patients undergoing aortic arch reconstruction

Purpose Our aim was to characterize changes in body temperatures during profound hypothermic cardiopulmonary bypass (CPB) conducted with the sternum opened.Methods In ten adult patients who underwent profound hypothermic (20°C) CPB for aortic arch reconstruction, pulmonary arterial temperature (PAT), nasopharyngeal temperature (NPT), forehead deep-tissue temperature (FHT), and urinary bladder temperature (UBT) were recorded every 1min throughout the surgery. In addition, the CPB venous line temperature (CPBT), a reasonable indicator of mixed venous blood temperature during CPB and believed to best reflect core temperature during stabilized hypothermia on CPB, was recorded during the period of total CPB.Results PAT began to change immediately after the start of cooling or rewarming, closely matching the CPBT (r = 0.98). During either situation, the other four temperatures lagged behind PAT (P 0.05); however, NPT followed PAT more closely than the other three temperatures (P 0.05). During stabilized hypothermia, PAT, NPT, and FHT, but not UBT, closely matched the CPBT, with gradients of less than 0.5°C.Conclusion During induction of profound hypothermia and its reversal on total CPB with the heart in situ, a PA catheter thermistor, presumably because of its placement immediately behind the superior vena cava, would provide a reliable measure of the mixed venous blood temperature. During stabilized profound hypothermia, PAT, NPT, and FHT, but not UBT, serve as a reliable index of core temperature.This work was presented, in part, at the 50th annual meeting of the Japanese Society of Anesthesiologists, Yokohama, May 29–31, 2003, and at the annual meeting of the American Society of Anesthesiologists, San Francisco, USA, October 11–15, 2003.     

Long-term pain relief effects in four patients undergoing percutaneous vertebroplasty for metastatic vertebral tumor

We reviewed long-term pain relief in four patients undergoing percutaneous vertebroplasty (PVP) for lumbar or back pain due to metastatic vertebral tumors. The patients received anesthesiological palliative care with analgesics until their death after PVP. Pain intensity, the presence or absence of recurrence of pain, changes in dosage of analgesics given before and after PVP, and complications associated with PVP were evaluated. A numerical rating scale (NRS) from 0 (no pain) to 10 (worst pain imaginable) was used to measure pain. The patients were three men and one woman (mean age, 58 years). PVP was performed in five vertebrae (one thoracic and four lumbar). The NRS scores on moving before PVP were 10, 8, 10, and 10. After PVP, NRS decreased to 0, 3, 5, and 0, respectively, within 72 h. No recurrence of pain in the treated area occurred until death in any of these patients. The dosages of analgesics given were decreased in two cases, but no changes were made in the other two cases. There were no complications associated with PVP. Percutaneous vertebro-plasty is a safe and effective treatment for long-time pain relief in patients with metastatic vertebral tumors.     

Surgical Treatment of Bone Metastasis Followed by a Primary Lung Cancer Lesion: Report of a Case

In August 1997, a 68-year-old man presented with right pelvic pain. Pelvic computed tomography (CT) and bone scintigraphy showed a huge tumor of the right iliac bone. No other lesion was detected, in spite of a high serum carcinoembryonic antigen level (CEA, 963ng/ml). In October 1997, the iliac bone tumor was widely resected, and thereafter was diagnosed to be a metastatic adenocarcinoma of unknown origin. After a resection, the serum CEA level dropped as low as 6.4ng/ml, but gradually went up to 80ng/ml in October 1999. Next, a lung tumor in the left upper lobe was detected by routine chest CT. In January 2000, a left upper lobectomy was performed, and based on not only the pathological findings but also on an immunohistochemical analysis for napsin A expression, the tumor was diagnosed to be lung adenocarcinoma. The histological and immunohistochemical findings in the previously resected bone lesion were completely compatible with those in the pulmonary tumor, which was finally regarded as M1 lung cancer. In October 2002, the patient was alive without any symptoms, although the serum CEA level was elevated again. We consider this case worthy of presentation because of its unique clinical course as well as the successful long-term survival after surgical treatment alone, for both the primary and metastatic lesions.     

D-Allose has a strong suppressive effect against ischemia/reperfusion injury: a comparative study with allopurinol and superoxide dismutase

Background/Purpose d-Allose, a rare sugar, is one of the potent inhibitors of ischemia/reperfusion injury of the rat liver. To investigate the potency of this powerful agent we examined its effect against ischemia/reperfusion injury and compared it to that of allopurinol and superoxide dismutase.Methods Male Lewis rats were given water ad libitum preoperatively for 12h and anesthetized by isoflurane inhalation anesthesia. Drugs were administered through a polyethylene catheter inserted into the portal vein for 2h (d-allose), 10min (allopurinol), or 5min (superoxide dismutase) before ischemia, and the livers were then subjected to 70% ischemia, induced by crossclamping the vessels to the lateral and median lobes of the liver for 90min. Rats were divided into four groups: group 1, pretreated with vehicle (normal saline); group 2, treated with d-allose; group 3, treated with allopurinol; and group 4, treated with superoxide dismutase. The effects of the drugs were evaluated by liver hemodynamics, neutrophil count, myeloperoxidase, liver enzymes, and histological studies.Results d-Allose improved liver hemodynamics (P < 0.001) and postischemic animal survival (P < 0.05) significantly compared with the control group and nonsignificantly compared with the allopurinol and superoxide dismutase groups. Myeloperoxidase activity in the postischemic liver tissue was decreased significantly (P < 0.05) by d-allose compared with all other treatment and control groups. Neutrophil count was also significantly (P < 0.05) decreased in the d-allose group compared with than that in the control group, as well as the superoxide dismutase group. Only d-allose produced a statistically significant decrease in the level of liver enzymes, compared with levels in the control group.Conclusions The moderately protective effect of d-allose, which caused no clinical side effects, is encouraging. d-Allose had the best protective effect against neutrophil-related postischemic injury of the liver tissue, followed by allopurinol and superoxide dismutase. However, a more extensive study is needed to ensure the effects as well as the mechanisms of the effect of this rare sugar.     

A Prospective Evaluation of Positron Emission Tomography Scanning,Sentinel Lymph Node Biopsy,and Standard Axillary Dissection for Axillary Staging in Patients with Early Stage Breast Cancer

Background: Positron emission tomography (PET) is a noninvasive imaging modality that can detect malignant lymph nodes. This study determined the sensitivity, specificity, predictive values, and likelihood ratios of PET scanning compared with standard axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB) in staging the axilla in women with early stage breast cancer.Methods: Women with clinical stage I or II breast cancer had whole body PET scanning before ALND and SLNB, in a prospective, blinded protocol. ALND were evaluated by standard hematoxylin and eosin (H&E) staining techniques, while sentinel nodes were also examined for micrometastatic disease.Results: A total of 98 patients were recruited. PET compared with ALND demonstrated sensitivity of 0.40 (95% CI, 0.16, 0.68), specificity 0.97 (CI, 0.90, 0.99), positive likelihood ratio 14.4 (CI, 3.21, 64.5), positive predictive value 0.75 (CI, 0.35, 0.97), and false–negative rate of 0.60 (CI, 0.32, 0.84). Test properties were similar for PET compared with sentinel nodes positive by H&E staining. A few false–positive scans (0.028, CI, 0.003, 0.097) were seen. Multiple logistic regression analysis found that PET accuracy was better in patients with high grade and larger tumors. Increased size and number of positive nodes were also associated with a positive PET scan.Conclusions: The sensitivity of PET compared with ALND and SLNB was low, whereas PET scanning had high specificity and positive predictive values. The study suggests that PET scanning cannot replace histologic staging in early stage breast cancer. The low rate of false–positive findings suggests that PET can identify women who can forego SLNB and require full axillary dissection.