Craniosynostosis in Twist heterozygous mice: A model for Saethre‐Chotzen syndrome

Saethre‐Chotzen syndrome is a common autosomal dominant form of craniosynostosis, the premature fusion of the sutures of the calvarial bones of the skull. Most Saethre‐Chotzen syndrome cases are caused by haploinsufficiency for the TWIST gene. Mice heterozygous for a null mutation of the Twist gene replicate certain features of Saethre‐Chotzen syndrome, but have not been reported to exhibit craniosynostosis. We demonstrate that Twist heterozygous mice exhibit fusions of the coronal suture and other cranial suture abnormalities, indicating that Twist heterozygous mice constitute a better animal model for Saethre‐Chotzen syndrome than was previously appreciated. Anat Rec 268:90–92, 2002. © 2002 Wiley‐Liss, Inc.     

Dose and dose rate effects of whole-body proton irradiation on leukocyte populations and lymphoid organs: part I.

The goal of part I of this study was to evaluate the effects of whole-body proton irradiation on lymphoid organs and specific leukocyte populations. C57BL/6 mice were exposed to the entry region of the proton Bragg curve to total doses of 0.5 gray (Gy), 1.5 Gy, and 3.0 Gy, each delivered at a low dose rate (LDR) of 1 cGy/min and high dose rate (HDR) of 80 cGy/min. Non-irradiated and 3 Gy HDR gamma-irradiated groups were included as controls. At 4 days post-irradiation, highly significant radiation dose-dependent reductions were observed in the mass of both lymphoid organs and the numbers of leukocytes and T (CD3(+)), T helper (CD3(+)/CD4(+)), T cytotoxic (CD3(+)/CD8(+)), and B (CD19(+)) cells in both blood and spleen. A less pronounced dose effect was noted for natural killer (NK1.1(+) NK) cells in spleen. Monocyte, but not granulocyte, counts in blood were highly dose-dependent. The numbers for each population generally tended to be lower with HDR than with LDR radiation; a significant dose rate effect was found in the percentages of T and B cells, monocytes, and granulocytes and in CD4(+):CD8(+) ratios. These data indicate that mononuclear cell response to the entry region of the proton Bragg curve is highly dependent upon the total dose and that dose rate effects are evident with some cell types. Results from gamma- and proton-irradiated groups (both at 3 Gy HDR) were similar, although proton-irradiation gave consistently lower values in some measurements.     

Cancer risk following appendectomy for acute appendicitis (Denmark)

Objective: Epidemiologic studies have not been able definitely to exclude that appendectomy carries a cancer risk. This study was conducted to clarify whether appendectomy is associated with a subsequent increase in cancer risk, since appendectomy is frequently an elective procedure. Methods: The present study included more than 82,000 persons who underwent appendectomy for acute appendicitis during 1977-89 according to the nation-wide Danish Hospital Discharge Register. During a follow-up interval of up to 17 years, cancer incidence was assessed by linkage to the Danish Cancer Registry and compared with the incidence in the general population of Denmark. Results: The total number of malignancies among appendectomized persons was 1.05 times higher than expected with 95 percent confidence intervals of 0.99-1.11. There was no clear significant excess of any specific cancer type. Conclusion: During a postsurgery period of nearly two decades, results of our study did not support the hypothesis that either appendectomy or acute appendicitis are likely to be associated with malignant neoplasms.     

Dietary factors and the risk of squamous cell esophageal cancer among black and white men in the United States

Objectives: To investigate dietary factors for squamous cell esophageal cancer and whether these factors may contribute to the five-fold higher incidence of this cancer in the black versus white population of the United States.Methods: Data from a food frequency questionnaire were analyzed for 114 white men and 219 black men with squamous cell esophageal cancer, and 681 white and 557 black male controls from three areas of the United States who participated in a population-based case-control study of esophageal cancer.Results: Protective effects were associated with intake of raw fruits and vegetables (odds ratio for high versus low consumers=0.3 in both white and black men) and use of vitamin supplements (especially vitamin C; odds ratio for high versus low consumers=0.4 in both races), with the frequency of consumption of raw fruits and vegetables and vitamin supplements being greater for white than black controls. In addition, elevated risks were associated with high versus low intake of red meat (OR=2.7 for blacks and 1.5 for whites) and processed meat (OR=1.6 for blacks and 1.7 for whites), with the levels of consumption being greater for black than white controls.Conclusions: In the United States, these dietary factors may contribute in part to the much higher incidence of squamous cell esophageal cancer among black compared to white men.     

Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples.

The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% CI, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL.     

Risk for anogenital cancer and other cancer among women hospitalized with gonorrhea

BACKGROUND: We investigated the relationship between infections with Neisseria gonorrhoeae and anogenital and other cancers. METHODS: Nationwide and population based register linkage study utilizing prospectively notified information. The observed numbers of cancers among the women were compared with those expected on the basis of national incidence rates. RESULTS: In a cohort of 4440 women hospitalized for gonorrhea we observed a total of 227 cases of cervical intraepithelial neoplasia grade III (CIN III), with 103 expected (standardized incidence ratio (SIR), 2.2; 95% confidence interval (CI), 1.9-2.5). No significantly increased risk for other anogenital cancers or cancer at other sites was seen. CONCLUSIONS: These results support the view that the observed association between gonorrheal infection and subsequent cervical preneoplasia is due mainly to surveillance bias. However, our results also indicate that women hospitalized with a N. gonorrhoeae infection will benefit from the compliance with the regular Pap smear screening programs.     

Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up

Although preservation of the spleen following abdominal trauma and spleen-preserving surgical procedures have become gold standards, about 22,000 splenectomies are still conducted annually in the USA. Infections, mostly by encapsulated organisms, are the most well-known complications following splenectomy. Recently, thrombosis and cancer have become recognized as potential adverse outcomes post-splenectomy. Among more than 4 million hospitalized USA veterans, we assessed incidence and mortality due to infections, thromboembolism, and cancer including 8,149 cancer-free veterans who underwent splenectomy with a follow-up of up to 27 years. Relative risk estimates and 95% confidence intervals were calculated using time-dependent Poisson regression methods for cohort data. Splenectomized patients had an increased risk of being hospitalized for pneumonia, meningitis, and septicemia (rate ratios=1.9–3.4); deep venous thrombosis and pulmonary embolism (rate ratios=2.2); certain solid tumors: buccal, esophagus, liver, colon, pancreas, lung, and prostate (rate ratios =1.3–1.9); and hematologic malignancies: non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia (rate ratios =1.8–6.0). They also had an increased risk of death due to pneumonia and septicemia (rate ratios =1.6–3.0); pulmonary embolism and coronary artery disease (rate ratios =1.4–4.5); any cancer: liver, pancreas, and lung cancer, non-Hodgkin lymphoma, Hodgkin lymphoma, and any leukemia (rate ratios =1.3–4.7). Many of the observed risks were increased more than 10 years after splenectomy. Our results underscore the importance of vaccination, surveillance, and thromboprophylaxis after splenectomy.