Effect on growth parameters of bone marrow transplantation with a chemotherapy-only conditioning regimen

INTRODUCTION: The increasing use of bone marrow transplantation (BMT) has increased survival among a growing number of children and young adults afflicted by malignant and nonmalignant hematologic disorders. Accordingly, quality of life has emerged as an important issue. Because they are a concern in this group, we assessed growth and development, following chemotherapy-only conditioning regimens. MATERIALS AND METHODS: Twelve prepubertal children (8 boys, G(1)P(1) and 4 girls, B(1)P(1)) with a mean age of 6 +/- 2 years (age range: 3.5 to 10 years) before and at 3, 6, 9, and 12 months post-BMT. RESULTS: Growth velocity at 1 year posttransplant was 10.0 +/- 3.5 cm/y. One year post-BMT, the statistical deviation saturation for growth velocity was 4.31 +/- 4.21. Height standard deviation score was -1.4 +/- 1.2 before and -0.5 +/- 1.3 1 year post-BMT (P <.004). The average weight of our subjects was 20 +/- 6 kg before and 26 +/- 9.5 kg 1 year post-BMT. DISCUSSION: BMT with a chemotherapy-only conditioning regimen not only does not disturb growth in children; it is actually associated with a relative growth spurt afterward.     

The risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves' orbitopathy

PURPOSE: In order to estimate the risk of radiation-induced carcinogenesis after external beam radiotherapy of Graves' orbitopathy, we made dosimetric measurements with thermoluminescent dosimeters in a male Rando phantom using our treatment technique. METHODS: We produced dose-volume histograms from 5-mm CT slices using our treatment planning system. In this way we estimated the irradiation dose received by the main surrounding organs such as the brain, the bone and the eyeball. We use 6-MV X-ray for the treatment of Graves' orbitopathy and our total dose is 2,000 cGy, 200 cGy per fraction. Clinical target volume was limited to the retrobulbar orbital content and medial rectus muscle, sparing the lenses, lacrimal glands and the sella turcica. All dosimetric measurements with thermoluminescent dosimeters were made 3 times. RESULTS: We found that the dose to the right lens was 101.6 mGy and to left lens 103.4 mGy. Average absorbed doses to red bone marrow, thyroid, lung, esophagus, bone surface, skin and brain, respectively, were estimated to be 523, 21, 4, 5, 81, 29, 47 mGy. Then, using tissue weighting factors specified by the International Commission of Radiation Protection, the resulting total effective dose was calculated to be 66.8 mSv. CONCLUSION: The risk factor for fatal cancer development derived from human epidemiological data is presently assumed to be 10% per Gy. In patients treated by our method of retro-orbital external beam radiotherapy for Graves' orbitopathy, there is a 0.0067 (or 7 per 1,000 persons or 0.7%) risk of developing fatal radiation-induced cancer.     

Comparison of alpha-stat and pH-stat cardiopulmonary bypass in relation to jugular venous oxygen saturation and cerebral glucose-oxygen utilization

Jugular venous oxygen saturation (SJVO(2)) reflects the balance between cerebral blood flow and metabolism. This study was designed to compare the effects of two different acid-base strategies on jugular venous desaturation (SJVO(2) <50%) and cerebral arteriovenous oxygen-glucose use. We performed a prospective, randomized study in 52 patients undergoing cardiopulmonary bypass (CPB) at 27 degrees C with either alpha-stat (n = 26) or pH-stat (n = 26) management. A retrograde internal jugular vein catheter was inserted, and blood samples were obtained at intervals during CPB. There were no differences in preoperative variables between the groups. SJVO(2) was significantly higher in the pH-stat group (at 30 min CPB: 86.2% +/- 6.1% versus 70.6% +/- 9.3%; P < 0.001). The differences in arteriovenous oxygen and glucose were smaller in the pH-stat group (at 30 min CPB: 1.9 +/- 0.82 mL/dL versus 3.98 +/- 1.12 mL/dL; P < 0.001; and 3.67 +/- 2.8 mL/dL versus 10.1 +/- 5.2 mL/dL; P < 0.001, respectively). All episodes of desaturation occurred during rewarming, and the difference in the incidence of desaturation between the two groups was not significant. All patients left the hospital in good condition. Compared with alpha-stat, the pH-stat strategy promotes an increase in SJVO(2) and a decrease in arteriovenous oxygen and arteriovenous glucose differences. These findings indicate an increased cerebral supply with pH-stat; however, this strategy does not eliminate jugular venous desaturation during CPB. IMPLICATIONS: A prospective, randomized study in 52 patients during cardiopulmonary bypass revealed that pH-stat increased jugular venous oxygen saturation and decreased arteriovenous oxygen-glucose differences. There was no difference in the incidence of jugular venous desaturation. These findings suggest an increased cerebral blood flow with no protection against jugular venous desaturation during pH-stat.     

Reversible acute renal failure associated with hypothyroidism: report of four cases with a brief review of literature

SUMMARY:   We present four adult cases of acute renal failure associated with hypothyroidism. All patients presented with symptoms suggestive of moderate to severe hypothyroidism, such as cold intolerance, constipation, muscle weakness, and lower extremity oedema. Initial serum creatinine levels ranged between 115 and 203 µmol/L (1.3 and 2.3 mg/dL), with creatinine clearances (CrCl) ranging between 0.58 and 0.97 mL/s (34.5 and 58 mL/min). After 6–12 weeks of treatment with levothyroxin, serum creatinine levels decreased to the range of 80 and 124 µmol/L (0.9 and 1.4 mg/dL) and CrCl increased to 0.74–1.64 mL/s (44–98 mL/min). One patient had proteinuria of 800 mg/day, which decreased to the normal range (<200 mg/day) after levothyroxin treatment. One patient developed acute gouty arthritis before normalization of thyroid-stimulating hormone (TSH), which was successfully managed with prednisone therapy. All of our patients had increased creatine kinase (CK), ranging between 1000 and 2360 U/L (normal range, 22–165 U/L), which normalized after 6 weeks of levothyroxin treatment.     

Stroke unit versus neurology ward

Abstract. Introduction: Few studies have tested the hypothesis of whether the beneficial effect of Stroke Units (SUs) can be reproduced in routine clinical practice and whether SU are also superior to neurological wards [NWs]. We aimed to compare the outcomes of patients of a newly implemented SU to the outcomes of patients hospitalized in a NW. Methods: We made a before-after comparison of 352 SUs and 352 NWs patients after adjusting for case-mixes by the multivariate method. Subgroup analyses were also performed to evaluate which patient groups benefit the most. In-hospital case-fatality, proportion of independent patients at discharge, length of hospital stay (LOHS), medical complication rate were the main outcome measures. Results: Adjusted in-hospital case fatality was significantly reduced in the SUs (OR: 0.44, 95 % CI: 0.26–0.76; p = 0.003). The proportion of independent patients at discharge and patients having medical complications was not different. Length of hospital stay was shorter in SU patients (13.76 days vs. 16.72 days, p = 0.003). Treatment in the SUs decreased case fatality in many subgroups [men, elderly, early admitted, severe stroke, co-morbidity present and ischemic stroke groups]. Discussion: The results of randomized trials in favor of SUs can be reproduced in routine clinical practice. The benefit of SU care seems to be more apparent with advancing age and increasing stroke severity. Stroke Unit seems to be a better alternative to an experienced NW.     

The frequency of founder mutations in the BRCA1, BRCA2, and APC genes in Australian Ashkenazi Jews: implications for the generality of U.S. population data

BACKGROUND: Several studies have shown that Ashkenazi Jews in the United States and Israel have a high prevalence of the founder mutations BRCA1 185delAG, BRCA1 5382insC, BRCA2 6174delT, and APC I1307K at frequencies of 1.0--1.1%, 0.2--0.3%, 0.6--1.4%, and 6.1--7.0%, respectively. The objective of this study was to compare the prevalence of these alleles in the Australian Jewish population with that of U.S. Jews. Australian Jews have a different history of migration, with less opportunity for changes in allele frequency due to conversion or intermarriage with non-Jewish Australians. The results obtained therefore can be used to assess whether U.S. data can be generalized to other Jewish populations. SUBJECTS AND METHODS. Subject samples were ascertained through a screening program for Tay-Sachs disease as part of a community-based screening program in New South Wales and Victoria. DNA extracted from 1200 deidentified blood samples was tested using amplification refractory mutation system polymerase chain reaction. RESULTS: The allele frequencies found were as follows: BRCA1 185delAG 1.25% (95% confidence interval [CI], 0.62--1.88%), BRCA1 5382insC 0.25% (95% CI, 0--0.53%), BRCA2 6174delT 1.08% (95% CI, 0.50--1.67%), and APC I1307K 8.67% (95% CI, 7.07--10.26%). The prevalence of breast carcinoma predisposition alleles therefore is greater than 2.5% in Australian Ashkenazim. CONCLUSIONS: There were no significant differences between the allele frequencies in Australian Ashkenazim and those identified in other studies with similar ascertainment strategies, despite the different migration patterns of Australian Jews. This suggests the broad applicability of the U.S. and Israeli data, not only to Australian Ashkenazim, but also to Ashkenazi communities throughout the world.     

Orthotopic liver transplantation for autoimmune hepatitis and cryptogenic chronic hepatitis in children

BACKGROUND: Autoimmune hepatitis (AIH) and cryptogenic chronic hepatitis (CCH) are important causes of liver failure in children, frequently necessitating orthotopic liver transplantation (OLT). The aim of this study is to review disease progression and potential differences between subgroups of children with AIH and CCH. METHODS: The medical records of 65 children diagnosed with AIH or CCH between 1980 and 1998 were evaluated. RESULTS: The median age at presentation was 9 years, 8 months (range 4 months-19 years), and the median follow-up period was 8 years (range 3 months-18 years, 10 months). Forty-one patients (63%) were female. Twenty-eight patients were Hispanic, 28 were Caucasian, 8 were African-American, and 1 was Asian. Forty-three patients (66%) were diagnosed with type 1 AIH, 8 (12%) with type 2 AIH, and 14 (22%) with CCH. Forty patients (62%) underwent OLT (51% of those with type 1 AIH, 75% of those with type 2 AIH, and 86% of those with CCH). Thirteen (33%) of the transplanted patients experienced disease recurrence. African-American patients experienced a significantly higher rate of disease recurrence post-OLT than did Hispanic patients. Seven patients (11%) died, two without OLT, and five posttransplantation. CONCLUSIONS: AIH and CCH frequently necessitate OLT in children. CCH is a more aggressive disease than Type 1 AIH among children with these disorders. Ethnicity influences the rate of disease recurrence after liver transplantation.     

Bystander effect in uracil phosphoribosyltransferase/5-fluorouracil-mediated suicide gene therapy is correlated with the level of intercellular communication

We examined whether a suicide gene/prodrug system using the uracil phosphoribosyltransferase (UPRT) of E. coli origin and 5-fluorouracil (5-FU) could achieve a bystander effect in two rodent tumor cell lines, murine colon carcinoma (Colon 26) and rat gliosarcoma (9L) cells. Cytotoxicity tests of mixed populations consisting of parent and transduced cells showed that the bystander effect was not produced in Colon 26 cells in either the UPRT/5-FU system or the herpes simplex virus-thymidine kinase/ganciclovir system but a strong bystander effect was evidenced by both suicide gene systems in 9L cells. The expression level of connexin 43, a protein that constitutes gap junctions, was high in 9L but low in Colon 26 cells. A gap junction-permeable fluorescein dye could be transferred among 9L cells but hardly at all among Colon 26 cells. Taken together, the efficacy of the bystander effect in the UPRT/5-FU system can be affected by gap junction-mediated intercellular communication.     

Cervical cerclage for prevention of preterm birth in women with twin pregnancy.

OBJECTIVE: To compare the effect of elective cervical cerclage in women with twin pregnancy on gestational age at time of delivery. METHOD: In a pragmatic fashion women in Abha Maternity Hospital, Saudi Arabia with twin gestations were allocated to receive either an elective cerclage (group I) or no cerclage (group II). Elective cerclage was performed at 12 to 14 weeks of gestation after sonographic examination of the fetus to confirm gestational age and exclude major congenital anomalies. In all cases, follow up of the pregnancy was continued until delivery. RESULTS: Of the 176 twin pregnancies included, cerclage was performed in 76 women, and no cerclage in 100 women. In Group I: 12 pregnancies ended in spontaneous miscarriage, 37 in preterm labor, and 27 women reached full term. There were a total of 106 live births in 62 women. In Group II: 8 women aborted, 44 women ended in preterm labor and 48 women reached full term. There were a total of 160 live births in 89 women. The gestational age at delivery ranged from 20 to 41 weeks. Multiple regression analysis did not show association between cerclage and time of delivery, although a trend was observed (P=0.056). CONCLUSION: Elective cerclage contributes little in prolongation of gestational age at the time of delivery in women with twin pregnancy, especially in women of high parity. Those with a previous history of preterm labor may be a subgroup that could benefit from elective cerclage.