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Biomedical subjects

L Ries

Publications and source records attributed to L Ries.

At least 19 recordsLinked to original sources
PubMed2001

Genetic analysis of Brugada syndrome in Israel: two novel mutations and possible genetic heterogeneity.

Idiopathic ventricular fibrillation in patients with an electrocardiogram (ECG) pattern of right bundle branch block and ST-segment elevation in leads V1 to V3 (now frequently called Brugada syndrome) is associated with a high incidence of syncopal episodes or sudden death. The disease is inherited as an autosomal dominant trait. Mutations in SCN5A, a cardiac sodium channel gene, have been recently associated with Brugada syndrome. We have analyzed 7 patients from Israel affected with Brugada syndrome. The families of these patients are characterized by a small number of symptomatic members. Sequencing analysis of SCN5A revealed two novel mutations, G35S and R104Q, in two Brugada patients, and a possible R34C polymorphism in two unrelated controls. No mutations were detected in 5 other patients, suggesting genetic heterogeneity. Low penetrance is probably the cause for the small number of symptomatic members in the two families positive for the SCN5A mutations.

Adult↗
PubMed2000

Prenatal diagnosis of a novel COL1A1 mutation in osteogenesis imperfecta type I carried through full term pregnancy.

Prenatal diagnosis was performed in a family where the father has osteogenesis imperfecta (OI) type I, with a novel mutation in the COL1A1 gene: a C to T change at position c3076 (c.3076C-->T) leading to a change of arginine at codon 848 to a stop codon (R848X). Prenatal diagnosis by chorionic villous sampling (CVS) was performed during the fourth pregnancy, and revealed that the fetus is a carrier of the same COL1A1 mutation. The possibility of phenotypic variability was discussed with the parents. They elected to carry the pregnancy to term, and a male child with mild OI was born. This is the first reported case where OI was diagnosed prenatally, and the parents opted to carry the pregnancy to term. It illustrates the potential use of DNA-based analysis for early prenatal diagnosis of OI, and the complexities of genetic counselling.

Adult↗
PubMed2000

Achondroplasia in diverse Jewish and Arab populations in Israel: clinical and molecular characterization.

BACKGROUND: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases. OBJECTIVES: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel. METHODS: We examined the G380R mutation (G > A and G > C transition) and the mutation G375C (G > T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia. RESULTS: We found the G > A transition at codon 380 in 30 of our patients and the G > C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia. CONCLUSIONS: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

Achondroplasia↗
PubMed1999

Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies.

Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso-enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso-enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses.

Alkaline Phosphatase↗
PubMed1997

A missense mutation in ColA1 in Jewish Israeli patient with mild osteogenesis imperfecta, detected by DGGE.

Osteogenesis imperfecta (OI) underlies germline mutations in either Col1A1 or Col1A2. Here we describe, for the first time, the use of the denaturing gradient gel electrophoresis (DGGE) technique for mutation analysis of the Col1A1 gene. By employing this technique, we identified a point mutation in a young Jewish Israeli patient with mild OI. The missense mutation, a G to A alteration at position 888, result in a Gly to Arg substitution at codon 79. Furthermore, the patient's mother, who was clinically labeled as OI based solely on the fact that she has blue sclera, was found not to carry this mutation in two different tissues. We suggest that blue sclera alone should not be used as a parameter for the diagnosis of OI, and that DGGE can be effectively used for mutation analysis of the Col1A1 gene.

Adult↗
PubMed1996

United States lung carcinoma incidence trends: declining for most histologic types among males, increasing among females.

BACKGROUND: Lung carcinoma is now the most frequently diagnosed major cancer in the world and is also the most common cause of cancer deaths in males and females in the United States and worldwide. Based on trends in cigarette smoking and on analysis of lung cancer rates by birth cohort, it was predicted that a decline would occur in age-adjusted lung cancer rates, initially in males, and approximately 10 years later in females. We evaluated age-adjusted lung cancer incidence rates for changes in trends by race, sex and histologic type to determine if and when rates may have started declining. METHODS: We analyzed population-based incidence data from the National Cancer Institute's Third National Cancer Survey conducted between 1969 and 1971 and from the Surveillance, Epidemiology and End-results (SEER) program conducted between 1974 and 1991. Age-adjusted rates were plotted by time period using a logarithmic scale for the ordinate. We used regression methods for grouped time-to-response data to fit a model to the disease rate for age, and calendar year to estimate the calendar year of maximum disease rate. RESULTS: During this period, the overall age-adjusted lung cancer incidence rate rose from 37.8 to 68.2 per 100,000. Lung cancer rates in both white and black males climaxed around 1984 and declined subsequently. Furthermore, among white and black males, the rates of squamous cell carcinoma, small cell carcinoma, and large cell carcinoma declined after peaks in 1981 and 1982, 1986 and 1987, and 1986 and 1988, respectively. The rates for adenocarcinoma in black males peaked in 1987 whereas the rates in white males appeared to have plateaued between 1989 and 1991. Total lung cancer rates in males exceeded those in females, with rates in black males exceeding rates in white males. Age-adjusted lung carcinoma rates among white and black females continued to increase for all histologic types with the exception of large cell carcinoma among whites, bronchioloalveolar carcinoma among whites and blacks, and adenosquamous carcinoma among blacks. CONCLUSIONS: The cumulative effect of these trends has resulted in a plateau of total lung carcinoma incidence in all persons combined, and a decline might be expected soon, as has already been observed among males. Most of these changes reflect past cigarette smoking patterns. Demonstration of declines and tapering increases among several population subgroups suggests impending reductions in the incidence and mortality rate for this highly fatal cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1996

Effect of gravidity on maternal serum markers for Down's syndrome.

The effect of gravidity on maternal serum alpha-fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated in 27,592 women being screened for Down's syndrome. There was no difference in the median AFP level in primigravid and multigravid women, but the median hCG level in multigravid women was 5.9 per cent lower than in those tested in their first pregnancy (P < 0.0001) and the median uE3 level was 3.9 per cent lower (P < 0.0001). Among multigravid women, there was no material difference in hCG levels according to the number of previous pregnancies or livebirths, whereas uE3 levels declined steadily with increasing numbers. Both markers declined with advancing maternal age: for hCG this was an independent effect, but for uE3 it was due to the correlation between age and gravidity. Allowing for these effects will not greatly alter the Down's syndrome screening detection and false-positive rates.

Adult↗
PubMed1996

Down's syndrome screening marker levels following assisted reproduction.

Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1.09 and 0.92 multiples of the normal gestation-specific median (MOM) based on a total of 34582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1.05 MOM) and a significant decrease when Pergonal was used (0.93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0.92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Down's syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Biomarkers↗
PubMed1996

Second primary cancers after vulvar and vaginal cancers.

OBJECTIVE: Our objective was to examine the occurrence of second primary cancers after vaginal and vulvar cancers. STUDY DESIGN: Women in whom cancers of the vagina (in situ, n=461; invasive, n=888) and vulva (in situ, n=2898; invasive, n=2685) were diagnosed between 1973 and 1988 were identified from nine population-based cancer registries. Subjects were followed through 1989 for the development of a subsequent primary cancer. RESULTS: We found increased risks of all second cancers combined among women with cancer of the vulva (observed/expected in situ = 1.5; observed/expected invasive = 1.3) and vagina observed/expected invasive = 1.2). Most of the excess second cancers were smoking related (e.g., cancers of the lung, buccal cavity and pharynx, esophagus, nasal cavity and larynx) or related to infection with human papillomavirus (e.g., cervix, vulva, vagina, and anus). CONCLUSION: These associations indicate that the follow-up care of women with cancers of the vulva and vagina should involve efforts to promote smoking cessation. The data are also consistent with a common sexually related cause for cancers of the cervix, vulva, vagina, and anus.

Cohort Studies↗
PubMed1996

Cancer and comorbidity in older patients: a descriptive profile.

In 1992, the National Institute on Aging (NIA) and the National Cancer Institute (NCI) initiated a study to assess the prevalence of comorbid conditions in elderly patients with cancer. Seven cancer sites were selected for the study: breast, cervix, ovary, prostate, colon, stomach, and urinary bladder. This report on approximately 7600 patients in the study sample describes the NIA/NCI approach to developing information on comorbidity in elderly patients and addresses the chronic disease burden (i.e., comorbidity) and severity for six particular conditions: arthritis, chronic obstructive pulmonary disease (COPD), diabetes, gastrointestinal problems, heart-related conditions, and hypertension. Data on comorbidity were collected by abstracting information from hospital medical records. Patients were registered in six geographic areas of the NCI Surveillance, Epidemiology, and End Results (SEER) Program. A stratified random sample of patients aged 55 to 64, 65 to 74, and 75 years or older-with the index cancers were selected. Comorbidity data were matched with data from the conventional SEER monitoring system. Analyses showed that hypertension is the most prevalent condition and is also much more common as a current management problem rather than as history for the NIA/NCI SEER Study patients. Heart conditions varied slightly in the percentage of severity reported, but percentages for all tumors remained within a range of 13 to 26% for current and past categories. A similar range was observed for arthritis, with the higher percentage seen in the current problem category. For episodic complaints (e.g., gastrointestinal problems), a medical history was more common, except for cancers that involve complaints associated with the malignancy (e.g., colon and stomach cancers and, to a lesser extent, ovarian cancer). COPD and diabetes were less prevalent. Analyses currently under way will determine the impact of a patient's comorbidity burden on the cancer care continuum of diagnosis, treatment, and survival. The broad and independent effects of chronic conditions, singly and in combination, are being examined.

Age Distribution↗
PubMed1996

Second-trimester serum fluorescence polarization in patients who subsequently develop pregnancy-induced hypertension.

To determine whether the midtrimester serum lipid profile, as expressed by fluorescence polarization (FP) values, is decreased in patients who subsequently develop pregnancy-induced hypertension (PIH). Stored serum samples of normotensive patients who had undergone midtrimester biochemical screening for Down's syndrome were used in this case-control study. Forty patients who subsequently developed PIH comprised the study group, and were divided into subgroups with proteinuric PIH (P-PIH, n = 18) and those with nonproteinuric PIH (NP-PIH, n = 22). Sixty randomly selected patients who remained normotensive throughout pregnancy comprised the control. Serum total cholesterol (CL) and triglycerides (TG) were determined using enzymatic colorimetric kits. FP values were determined by optical microviscosimeter. Both study subgroups had significantly lower FP values and higher TG concentrations than the control group. Total CL concentrations were slightly higher in the P-PIH subgroup. There were no differences in mean. Total CL or TG concentrations or mean FP values were found between those patients who developed mild and severe PIH. Using FP value cutoff points of 0.250, 0.245, and 0.240 sensitivity was 95%, 90%, and 78%, respectively, in detecting patients who subsequently developed PIH. Midtrimester serum FP values may have some predictive value for the development of P- and NP-PIH.

Adult↗
PubMed1995

Cancer. Introduction.

This supplement presents the study of various histologic types of cancers diagnosed in the populations covered by the Surveillance, Epidemiology, and End Results (SEER) Program. It describes the SEER program and the coding of histologic type by the International Classification of Diseases for Oncology. Each of the 19 articles deals with the histologic types of cancer found in major sites or with specific histologic types, such as lymphomas or melanomas. Histologic types have been grouped based on those developed by Dr. John Berg. Data presented in this supplement are based on more than one million microscopically proven invasive cancers and 98,000 in situ cancers diagnosed during the period 1973-1987 in areas covered by the SEER Program.

Adolescent↗
PubMed1994

The National Institute on Aging and the National Cancer Institute SEER collaborative study on comorbidity and early diagnosis of cancer in the elderly.

BACKGROUND: An effect of comorbidity, or the coexistence of other diseases, on the stage of cancer at diagnosis and the appropriateness of therapy in older patients with cancer is hypothesized. The effect of comorbidity differs by cancer site and by type of comorbidity. Such variation could be due to the use of different populations or methods, or the natural history of the tumor being studied. METHODS: The National Institute on Aging (NIA) and the National Cancer Institute (NCI) have initiated a study using cancer patient populations in the NCI's SEER (Surveillance, Epidemiology and End Results) program. Five geographic locations participated in the NIA/NCI pilot study of comorbidity associated with seven cancer sites. Approximately 250 patients with each type of cancer, stratified by age (either 65-74 years of age or 75 years and older) had hospital records abstracted for comorbidity using a form derived from previously reported methods. RESULTS: After analyzing preliminary results for 1712 patients, it was ascertained that more and different chronic disease categories would be necessary, that it was not feasible to collect data on ability to perform certain physical functions from the medical records, and that the collection of data on current medications was possible. With these limitations, relationships of comorbid conditions with stage of cancer were analyzed. CONCLUSION: With the success of the pilot study, the full study is underway. In addition to the planned abstracting of approximately 7800 records, interviews assessing the behavior of illness in a sample of 1000 cancer patients will provide valuable information on the influence of comorbidity and age on stage at initial diagnosis and the treatment of older persons afflicted with cancer.

Aged↗
PubMed1994

The association between alpha-fetoprotein and beta hCG levels prior to and following chorionic villus sampling in cases that spontaneously miscarried.

Maternal serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta hCG) measurements taken prior to chorionic villus sampling (CVS) in 21 patients who subsequently miscarried were compared with measurements in a control group of 113 patients with uneventful pregnancies. Patients with AFP levels of 10 iu/ml or more prior to the CVS had a 4.3 times greater risk of miscarriage (95 per cent confidence interval 1.3-13.6). AFP levels obtained 1 week after the CVS in the 13 patients with late miscarriages were higher than in the control group (P = 0.06). Patients miscarrying had a greater rise in AFP (P = 0.06) and a greater fall in beta hCG levels (P = 0.04) following the CVS procedure, compared with the control subjects. Each 10-unit change in the difference between AFP or beta hCG levels prior to and 1 week following the CVS was associated with a significantly increased risk for late miscarriage. Elevated maternal serum AFP levels early in pregnancy and changes in AFP and beta hCG levels following CVS may predict an increased risk for subsequent miscarriage.

Abortion, Spontaneous↗
PubMed1993

Expanding multiple marker screening for Down's syndrome to include Edward's syndrome.

Information on maternal age and maternal serum alpha-fetoprotein, unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was used to investigate retrospectively the effect of estimating Edward's syndrome risk in women having multi-marker screening for Down's syndrome. The screened population comprised 15 pregnancies affected by Edward's syndrome, 15 with Down's syndrome and 5472 unaffected pregnancies. The use of all three markers to estimate Edward's syndrome risk would have led to the detection of 10-12 (67-80 per cent) cases with a false-positive rate of 0.3-0.6 per cent depending on the risk cut-off. A further case would have been detected as a result of screening for Down's syndrome alone. Similar results were obtained when the Edward's syndrome risk was based on uE3 and hCG only. These data suggest that extending Down's syndrome screening to include Edward's syndrome risk will yield a high detection rate with only a small increase in the false-positive rate.

Adult↗
PubMed1991

Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index.

Survival rates for 22,616 cases of breast cancer listed in the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute were stratified on outcome according to the histologic grade and stage of disease. Two different staging systems, "local, regional, and distant" and a modified American Joint Committee on Cancer (AJCC) system adopted for SEER were used. Relative survival rates were calculated at 5 and 10 years. Patients who were assigned Stage II, Grade 1 had the same survival as those assigned Stage I, Grade 3. Their survival was better than patients assigned Stage I, Grade 4. The 5-year relative survival rate for patients listed as Stage I, Grade 1 was 99% and for patients listed as Stage I, Grade 2, it was 98%. At 10 years, the survival rate of patients assigned Stage I, Grade 1 was 95%. Patients with histologic Grade 1 tumors less than 2 cm in size and with positive axillary lymph nodes had a 5-year survival rate of 99%. As breast tumors increased in size, the histologic grade also increased. The results suggest that in linking histologic grade with stage of disease, the staging system should also be considered. Histologic grade when used in conjunction with stage of disease can improve the prediction of outcome. Our results also indicate that a prognostic index can be created for breast cancer using a combination of stage of disease and histologic grade. The data suggest that only three grades are needed for breast cancer.

Adult↗