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PubMed1991

Resolution of vesicoureteral reflux in completely duplicated systems: fact or fiction?

A total of 60 patients (71 renal units) with grade 2/5 vesicoureteral reflux into the lower pole moiety of a completely duplicated system was managed by medical surveillance and is compared to an identically managed age, race and sex matched control population with a similar degree of reflux into a single collecting system. During a median 2-year observation period reflux ceased spontaneously in 10% of the patients with duplication compared to 35% of the control population (p less than 0.01). Comparisons between the 2 study groups failed to reveal a difference in the incidence of break-through urinary tract infections, advancing degrees of reflux and/or the development or progression of renal scarring (p greater than 0.5). Despite the fact that the resolution rate in duplex systems is significantly lower than that of a single system, it is apparent that cessation of grade 2/5 reflux into a duplicated ureter will occur and that a trial of medical management is an appropriate initial method of therapy.

Actuarial Analysis↗
PubMed2002

A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer.

CHEK2 (previously known as "CHK2") is a cell-cycle-checkpoint kinase that phosphorylates p53 and BRCA1 in response to DNA damage. A protein-truncating mutation, 1100delC in exon 10, which abolishes the kinase function of CHEK2, has been found in families with Li-Fraumeni syndrome (LFS) and in those with a cancer phenotype that is suggestive of LFS, including breast cancer. In the present study, we found that the frequency of 1100delC was 2.0% among an unselected population-based cohort of 1,035 patients with breast cancer. This was slightly, but not significantly (P=.182), higher than the 1.4% frequency found among 1,885 population control subjects. However, a significantly elevated frequency was found among those 358 patients with a positive family history (11/358 [3.1%]; odds ratio [OR] 2.27; 95% confidence interval [CI] 1.11-4.63; P=.021, compared with population controls). Furthermore, patients with bilateral breast cancer were sixfold more likely to be 1100delC carriers than were patients with unilateral cancer (95% CI 1.87-20.32; P=.007). Analysis of the 1100delC variant in an independent set of 507 patients with familial breast cancer with no BRCA1 and BRCA2 mutations confirmed a significantly elevated frequency of 1100delC (28/507 [5.5%]; OR 4.2; 95% CI 2.4-7.2; P=.0002), compared with controls, with a high frequency also seen in patients with only a single affected first-degree relative (18/291 [6.2%]). Finally, tissue microarray analysis indicated that breast tumors from patients with 1100delC mutations show reduced CHEK2 immunostaining. The results suggest that CHEK2 acts as a low-penetrance tumor-suppressor gene in breast cancer and that it makes a significant contribution to familial clustering of breast cancer-including families with only two affected relatives, which are more common than families that include larger numbers of affected women.

Breast Neoplasms↗
PubMed1994

Localization of motor areas adjacent to arteriovenous malformations. A positron emission tomographic study.

Motor cortex activity was localized with positron emission tomography (PET) in 4 patients with large arteriovenous malformations adjacent to or undercutting the left primary motor cortex. Relative cerebral blood flow responses were measured during execution of a visually guided motor tracking task performed with the right index finger, hand, great toe, tongue, or eyes alone (control) and mapped onto each patient's corresponding magnetic resonance imaging (MRI) scan. The relative cerebral blood flow responses in the contralateral precentral gyrus, adjacent to each arteriovenous malformation, demonstrated a normal somatotopic distribution, similar to that in a control population. In the 3 patients with preserved motor function, responses were also present in the ipsilateral primary motor cortex, bilateral supplementary motor area, and ipsilateral anterior cerebellum, similar in location to those of a control population. In the fourth patient with a hemiparesis, responses were attenuated in the primary motor cortex, increased in the supplementary motor area, and absent in the cerebellum. The results demonstrate that PET cerebral blood flow mapping can localize motor cortex despite the presence of significant blood flow abnormalities in adjacent arteriovenous malformations. The method, particularly when combined with MRI, may be used in the planning of surgical, radiation, or embolization therapy.

Adult↗
PubMed1991

Increased frequency of HLA-DR3 and complotype SC01 in Mexican mestizo patients with amoebic abscess of the liver.

Our preliminary study (31 patients) of HLA frequencies and amoebic abscess of the liver (AAL) in Mexican mestizos was extended to include 110 patients with this condition. The previously found increase in HLA-B16 was not confirmed, but the frequency of HLA-DR3 was again found significantly increased in patients with AAL when compared to the normal, ethnically matched control population, both in its isolated (35.5% vs 12.7%) and in the HLA-A2, DR3 haplotypic version (20.9% vs 4.5%). Moreover, seven of the 17 HLA specificities that were found to be individually different at P (yet not at PC) level in patients with AAL when compared to the control population, were actually HLA-DR3 containing haplotypes. HLA-DR3 may thus encode a risk factor(s) for AAL, at least in the Mexican mestizo population. Furthermore a significant increase in the complotype SC01 and its haplotypic version SC01, DR4 were identified in 45 non selected patients with AAL when compared to normal controls (31.1% vs 6.7% and 17.8% vs 0% respectively). Even though a relationship between allelic forms of complement components and their function has not been fully established, this complotype could represent a risk factor as well, since complement appears to play a role in host defence against amoebic invasion. Finally, no extended haplotype preference was found in these AAL patients.

Adult↗
PubMed2003

CHEK2 variants associate with hereditary prostate cancer.

Recently, variants in CHEK2 gene were shown to associate with sporadic prostate cancer in the USA. In the present study from Finland, we found that the frequency of 1100delC, a truncating variant that abrogates the kinase activity, was significantly elevated among 120 patients with hereditary prostate cancer (HPC) (four out of 120 (3.3%); odds ratio 8.24; 95% confidence interval 1.49-45.54; P=0.02) compared to 480 population controls. Suggestive evidence of segregation between the 1100delC mutation and prostate cancer was seen in all positive families. In addition, I157T variant had significantly higher frequency among HPC patients (13 out of 120 (10.8%); odds ratio 2.12; 95% confidence interval 1.06-4.27; P=0.04) than the frequency 5.4% seen in the population controls. The results suggest that CHEK2 variants are low-penetrance prostate cancer predisposition alleles that contribute significantly to familial clustering of prostate cancer at the population level.

Adult↗
PubMed1990

Increased frequency of 6-thioguanine-resistant lymphocytes in peripheral blood of workers employed in cyclophosphamide production.

The frequency of 6-thioguanine-resistant peripheral blood lymphocytes has been determined by autoradiography in a control population and a population of cyclophosphamide-exposed individuals. The mean variant frequency in a non-exposed population was found to be 2.76 +/- 1.48 X 10(-5). Subpopulations of smokers and non-smokers revealed statistically significant differences in the variant frequencies, i.e. 3.52 +/- 1.55 X 10(-5) and 2.07 +/- 1.05 X 10(-5) respectively. In 20 out of a total of 23 individuals employed in cyclophosphamide synthesis and manufacturing, the variant frequency of 6-thioguanine-resistant lymphocytes was found to be higher than the maximum individual frequency found in the control population. The mean variant frequency in the cyclophosphamide-exposed population was 13.64 +/- 13.56 X 10(-5), a statistically significant increase as compared to the mean control frequency. There was no correlation between variant frequency and duration of employment suggesting that this test reflects the actual exposure and not a cumulative effect.

Adult↗
PubMed2004

C34T AMP deaminase 1 gene mutation protects cardiac function in donors.

Dysfunction of the donor heart is an important clinical problem that could be affected by genetic factors. We tested the hypothesis that possession of the C34T nonsense mutation in AMPD1 gene, which is known to improve survival in chronic heart failure, protects against cardiac dysfunction in donors. Genetic analysis for C34T mutation was performed by single-stranded conformational polymorphism (SSCP) in 22 donor hearts used for transplantation, 10 unused donor hearts with acute heart failure (HF), 37 patients with chronic HF, and 207 healthy controls. We found a significantly higher frequency of the mutation among donors with healthy hearts used for transplantation (31.8%) as compared to control population (13.5%, P < 0.001) and a lower frequency in dysfunctional donor hearts (5.0% P = 0.025); the frequency of the C34T mutation in patients with chronic heart failure (14.8%) was not different from that of a control population. The presence of the C34T mutation in AMPD1 gene appears to be protective against acute heart failure in cardiac donors.

AMP Deaminase↗
PubMed1996

Anterior resection: do the patients perceive any clinical benefit?

PURPOSE: Functional results following anterior resection of the rectum have been sparsely reported. Results concerning stool frequency and continence vary widely. These variations may represent several areas of bias, but one of the main concerns is study design. Many studies are focused on physiological results and even when a control population is included in the study design, it is not used to compare the clinical functional outcome. the aims of this prospective study were: (1) to study serially before and 1 year after low anterior resection for carcinoma the changes in clinical function; and (2) to study if these changes could be attributable to the characteristics of the population, comparing the results with sex-matched and age-matched controls. MATERIAL AND METHODS: Sample size was previously established according the prevalence of continence disorders fund in two previous studies carried out in our country, 36% for anterior resection, and 6% among general population in our community. Thirty-eight consecutive patients (mean age 63.9 years, range 41-77 years) with a diagnosis of rectal carcinoma were invited to participate in the study. The lower margin of the tumor was located between 4 and 15 cm from the anal margin (median of level tumor 6.0 cm). A control group of 25 volunteers matched for sex and age with patients who were questioned 1 year after the anterior resection were also studied. Median level of anastomosis was 6.2 +/- 2.7 cm (range 2-11) above the anal margin. In six patients with an anastomosis less than 4 cm from the anal margin, a loop ileostomy was constructed and closed 3 months later. Patients were interviewed by a research assistant before and 1 year after operation or 1 year after closure of the temporary defunctioning loop ileostomy. Patients were questioned about bowel frequency over 24 h, urgency, tenesmus, erratic defecatory patterns, discrimination of bowel content and continence. RESULTS: Clinical function of patients before and after operation. Compared with pre-operative, bowel frequency of 3.9/day (range 0.3-14) did not differ significantly 1 year after operation at 2.3/day (range 0.5-6). Frequency of erratic defecatory patterns (44%), urgency (40%) and obstructed defecation (20%) did not differ between the preoperative and postoperative period. Forty-eight percent of patients suffered tenesmus and 20% were unable to discriminate between flatus and feces before operation, whereas these troublesome symptoms were present in 24% and 16%, respectively, after the operation. Before the operation 32% of patients reported fecal leaks while in the postoperative period 52% patients complained of this alteration. Clinical function of patients compared with controls. Patients had a mean stool frequency per day of 2.3 (range 0.5-6) and controls 1.3 (range 0.3-5). Forty-four percent of patients had erratic defecatory patterns, 24% suffered tenesmus and 40% urgency, whereas these troublesome symptoms were present in 12% in the control population. Moreover, obstructed defecation was present in 20% and 4%, respectively. All controls and 84% of patients maintained discrimination of flatus, liquid and solid feces. Fifty-two percent of patients and 8% of controls suffered from altered continence. CONCLUSIONS: One year after low anterior resection patients had poor bowel function when compared with a control population of the same age and sex. A distinct anterior resection syndrome exists consisting of increased bowel frequency, erratic defecatory patterns, urgency, tenesmus, obstructed defecation, and minor fecal leakage. Furthermore, these disturbances in defecatory function did not differ significantly from symptoms produced by the rectal carcinoma, and patients experienced no major benefit from surgery from a functional point of view.

Adult↗
PubMed1999

Prevalence of tumor necrosis factor-alpha and angiotensin converting enzyme polymorphisms in mild/moderate and fatal/near-fatal asthma.

Allele 2 of the polymorphism at position -308 in the promoter of the tumor necrosis factor alpha (TNF-alpha) gene, and the D allele of the angiotensin converting enzyme (ACE) gene, have been associated with asthma. We hypothesized that genotypes containing these alleles would show an increased prevalence in asthmatic as compared with nonasthmatic individuals, and would be associated with asthma severity. Polymerase chain reaction-based assays were developed to determine TNF-alpha and ACE genotypes among subjects with mild/moderate asthma (n = 92), fatal/near-fatal asthma (n = 159), no asthma (n = 43), and random population controls (n = 252). The TNF-alpha -308 polymorphism was increased in both subjects with mild/moderate (p = 0.03) and those with fatal/near fatal asthma (p = 0.02) versus those without asthma, and in all subjects with asthma versus random population controls (p = 0.02). The mild/moderate group was subdivided into subjects with mild (n = 43) and those with moderate (n = 33) asthma. TNF-alpha -308 was increased in the moderately asthmatic versus the nonasthmatic subjects (p = 0.003), and in the mildly asthmatic subjects (p = 0.01). However, TNF-alpha -308 was not significantly more prevalent in the fatal/near-fatal than in the mild/moderate asthmatic group. The ACE-D allele did not show an association with either asthma or asthma severity. We conclude that the TNF-alpha -308 polymorphism may be a risk factor for asthma but does not increase the risk of a fatal or a near-fatal asthma attack, whereas the ACE polymorphism is not associated with asthma in this population.

Adult↗
PubMed2002

Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children.

OBJECTIVE: To evaluate the isotype and IgG subclass distribution of anti-pneumococcal antibodies and response to polysaccharide vaccination in otitis prone children. METHODS: IgG1, IgG2 and IgA antibodies to pneumococcal serotypes 3, 4, 6B, 9V, 14, 19F and 23F were determined in otitis prone children and in an age-matched healthy control population. Patients were immunized with a 23-valent pneumococcal polysaccharide vaccine. The antibody response was measured 4 weeks later. RESULTS: Geometric mean IgA and IgG2 antibody levels for all seven pneumococcal serotypes tested were significantly lower in otitis prone children than in the control population. After immunization, there was no significant increase in geometric mean IgG2 anti-serotype 6B, 19F and 23F pneumococcal polysaccharide (weak immunogenic), but also no increase for IgG2 anti-serotype 4 and 14. Post immunization IgG2 antibody titers for serotypes 6B, 9V and 19F even remained below titers of non-vaccinated controls. Nine out of 29 otitis prone children were colonized nasopharyngeally with Streptococcus pneumoniae during the time of vaccination; these children had an even more severely impaired systemic antibody response. CONCLUSIONS: Otitis prone children, while having normal IgG1 antibody levels, have low IgG2 and IgA anti-polysaccharide antibody levels and fail to respond in these subclasses upon vaccination with pneumococcal polysaccharide vaccine.

Adenoidectomy↗
PubMed1985

Defective renal prostaglandin synthesis in hypertensive patients with morbid obesity.

Renal prostaglandin synthesis in 36 obese hypertensive patients was estimated from measurements of 24-hour urinary prostaglandin E2 (PGE2) excretion rates. PGE2 was measured by radioimmunoassay using Dray antiserum prior to and 1 week after starting a fast supplemented by 320 cal derived from 30 g of carbohydrate, 45 g protein, and 2 g essential fatty acids. Sodium intake was 120 mEq daily or less. Comparisons were made to a control population of age-matched, nonobese, normotensive, healthy volunteers on a normal diet. Mean weight fell from 260 +/- 8 to 247 +/- 8lb, p less than 0.001. Urinary PGE2 in the obese patients prior to the fast was 104 +/- 27 ng/day, significantly lower than the 404 +/- 124 ng/day found in the control population, p less than 0.005. After the 1st week of the fast urinary PGE2 rose to 213 +/- 55, p less than 0,02. This value was not different from that in the control group. Blood pressure fell (p less than 0.001) in these patients from 143/94 +/- 3/2 to 134/87 +/- 3/2 mm Hg after the 1st week of the fast. Deficient renal prostaglandin synthesis in obese hypertensive patients was corrected by fasting. Such changes in the prostaglandin system may mediate or occur in response to changes in the sodium-volume balance of these patients. These changes in renal prostaglandin synthesis may partly contribute to the blood pressure reduction of these patients.

Blood Pressure↗
PubMed1995

Interictal abnormalities of regional cerebral blood flow in migraine with and without aura.

Some controversial issues exist whether regional cerebral blood flow (rCBF) changes are present both in migraine with and without aura during the interictal period. For this reason we have studied rCBF characteristics in migraine patients when headache-free. rCBF examinations were performed by the 133Xe inhalation method on 39 normal subjects (24 aged 45 or less and 15 older than 45), on 10 migraine patients with (A+) and on 10 without (A-) aura. The values of each patient were compared with the age-matched control population mean by a computer-assisted mapping system that allows statistical analysis in real time. To compare inter-individual variability 10 subjects, out of 39 normals, constituted an age-, sex- and CO2-matched control group (C). 8 A+ patients and 7 A- showed significant alterations of CBF in comparison with the age-matched control population. The analysis between the age-, sex- and CO2 matched groups showed significant differences of the inter-hemispheric (F = 6.669, p = 0.004) and of the frontal (F = 7.480 p = 0.0008) asymmetries. These data show that in the headache-free period a derangement of the cerebral perfusion is present in both migraine with and without aura, suggesting they are due to the same disease process. Furthermore they show the usefulness of a computer-assisted mapping system, suitable for clinical use, in discovering small alterations in cerebral perfusion.

Adult↗
PubMed2002

Evaluation of genotoxic effects in a group of workers exposed to low levels of styrene.

Occupational exposure to styrene was studied in a group of workers engaged in the production of fiberglass-reinforced plastics. Sister-chromatid exchanges (SCE), micronuclei (MN), and DNA damage (evaluated by means of comet assay) were measured in peripheral blood cells from the exposed workers and from a control population. Mandelic acid concentration, an indicator of styrene exposure level, was measured in urine samples collected at the end of the work shift. Average estimated values for styrene exposure were slightly below the threshold limit value (TLV) of 20 ppm recommended by the American Conference of Governmental Industrial Hygienists. Significant increases (P< or =0.01) have been found for SCE and MN frequencies and comet tail length among exposed individuals, as well as significant decreases (P< or =0.01) in the proliferation indices, as compared with control population. High correlation has been obtained between endpoints evaluated and exposure length, and increased values of SCE and MN frequencies and comet tail length have been found among smokers only in the exposed population. The high correlation obtained among SCE and MN frequencies and comet tail length, and the increase of these parameters in the exposed group with regard to control group justify the use of these three biomarkers in the evaluation of genotoxic effects in human populations exposed to styrene.

Age Factors↗
PubMed2001

Treatment of morbid obesity in inner-city women.

OBJECTIVE: To explore the use of the very-low-calorie formula diet (VLCD) in the indigent population of Newark, NJ, with the goal of achieving 10% weight loss within a relatively short period of 10 weeks. RESEARCH METHODS AND PROCEDURES: We accepted 131 morbidly obese indigent women into our study program. The study was limited to women only and the average starting weight was 292.3 +/- 5.9 lbs (+/- SE; 50.3 +/- 0.9 body mass index [kg/m(2)]). We used three treatment paradigms: total cost-free program for 10 weeks; cost-free, but compliance requirements; and a weekly charge of $25. The results obtained were compared with two control populations: women enrolled during the same recruitment period in a comparable suburban VLCD program and a historical control population of suburban women treated from 1985 through 1995. RESULTS: In group A (total cost-free), 79% of patients completed the 10-week program, but only 18% of patients achieved the goal of 10% weight loss. In group B when attendance and weight loss requirements were imposed, the dropout rate accelerated such that only 37% of patients completed the 10-week course, and 16% of the women were successful with their weight loss. In group C, imposing $25/wk financial outlay also accelerated dropouts but had little effect on weight loss success, which was 10% of the starting group. By comparison, the suburban patients and the historical control group exhibited 67% and 76% attendance rates after 10 weeks, and 33% and 55% success rates, respectively, in achieving the weight loss goal. DISCUSSION: We conclude that inner-city patients exhibit great interest in weight loss when financial barriers are removed. Successful weight loss was achieved in 10% to 18% of patients using the VLCD approach, approximately one-half of that obtained in affluent suburban women. Imposing financial or compliance restrictions to the inner-city patients served only to enhance dropouts.

Adult↗
PubMed1993

The use of restricted controls to prevent recall bias in case-control studies of reproductive outcomes.

Recall bias or report bias is said to occur when associations are distorted or created because case informants report events differently from controls. Some investigators have suggested that this bias can be prevented by choosing controls who have conditions similar to those found in the case group. We use the term "restricted-control group" for such a control series. Although using a restricted-control series may eliminate differential misclassification, this approach will usually not eliminate nondifferential misclassification and may create selection bias. In this article, we present a way to algebraically examine the effects of misclassification and selection bias on observed associations. We use this method to compare the impact of recall bias in a study using a population control group with the effects of selection bias and nondifferential misclassification if a restricted-control group is used. Our approach is exemplified using data from a case-control study of sudden infant death syndrome. Our findings show that even when recall bias exists, the observed association can be closer to the true association when a population control series is used than when a restricted-control group is used.

Bias↗
PubMed2005

Polymorphism of Slc11a1 (Nramp1) gene and canine leishmaniasis in a case-control study.

The prevalence of canine leishmaniasis infection in an endemic area such as the Mediterranean basin (67%) is higher than the prevalence of the disease (10%), suggesting a role of host genetics related to the outcome of the disease. Because Slc11a1 gene affects susceptibility and clinical outcome of autoimmune and infectious diseases, we analyzed five polymorphisms of the Slc11a1 gene in a case-control study with 97 dogs: three new single nucleotide polymorphisms and a G-stretch in the promoter and a microsatellite in intron 1. Haplotype frequency distributions showed significant differences between case and control populations (P = .01), most likely owing to the single nucleotide polymorphisms in the promoter region that were associated to case dogs. The most frequent haplotypes included TAG-8-141, which was present in all the breeds, in both case and control animals; and TAG-9-145, which was overrepresented in the control population and mostly found in boxer dogs. Within the boxer breed, 81% of the healthy dogs were homozygous TAG-9-145, whereas TAG-8-141 was significantly associated to case boxers (P = .02). The special genotype distribution for the Slc11a1 polymorphism associated with the prevalence of the illness in the boxer breed emphasizes the potential importance that breed genetic background has in canine leishmaniasis susceptibility.

Animals↗
PubMed1989

Cancer risks due to occupational exposure to formaldehyde: results of a multi-site case-control study in Montreal.

A case-control study was undertaken in Montreal to investigate the possible associations between occupational exposures and cancers of the following sites: oesophagus, stomach, colo-rectum, liver, pancreas, lung, prostate, bladder, kidney, melanoma and lymphoid tissue. In total, 3,726 cancer patients and 533 population controls were interviewed to obtain detailed lifetime job histories and information on potential confounders. Each job history was translated into a history of occupational exposures. Because of current concerns about formaldehyde carcinogenicity, we carried out a special analysis of the association between exposure to formaldehyde and each type of cancer covered by this study. Separate statistical analyses were carried out for each type of cancer using population controls as well as a control series drawn from among the other cancer sites in the study. Although nearly a quarter of all subjects had undergone occupational exposure to formaldehyde, the levels of exposure were in general quite low. There was no persuasive evidence of an increased risk of any type of cancer among men exposed to these levels of formaldehyde. However, the possibility of a small increase in risk could not be ruled out.

Adult↗
PubMed1989

Anti-hypertensive drugs non-specifically reduce "spontaneous" activation of blood platelets.

Abnormal activation of blood platelets may be a contributory factor in the accelerated vascular disease which occurs in hypertension. We investigated the effects of lowering blood pressure in 12 patients with mild hypertension on several aspects of platelet function, initially in a placebo-controlled, double-blind, cross-over study with nisoldipine, and subsequently in the same patients comparing nisoldipine with the patients' usual anti-hypertensive therapy. Values were compared with those from an age, sex-matched control population. Seven hypertensive patients with renal failure were also studied. Administration of nisoldipine reduced ex vivo "spontaneous" aggregation of blood platelets significantly, and a similar significant effect was seen when blood pressure was lowered by the patients usual anti-hypertensive therapy. "Spontaneous" aggregation occurring in the control population was similar to that in the treated hypertensives. Blood platelet count, and aggregation in response to ADP and adrenalin were unaffected by treatment. Median plasma beta thromboglobulin levels were significantly higher in the untreated hypertensive patients (43 ng ml-1) than in the controls (30 ng ml-1), and there was a trend to reduced values for beta thromboglobulin on treatment of the hypertension. These results indicate that blood platelet activity is enhanced in hypertension and that function returns towards normal when blood pressure is lowered by treatment.

Adult↗