The LEP gene and age of menarche: maternal age as a potential cause of hidden stratification in association studies.

Leptin has a powerful effect on fertility and the initiation of puberty in addition to its effect on obesity. It has been suggested that that in times of fasting, infertility induced by low leptin levels protect the female from the energy demands of pregnancy. Despite this there have been no studies of the potential role of LEP gene variants on the age of onset of menarche. We genotyped 183 non-Hispanic Caucasian adult females at the LEP D7S1875 dinucleotide repeat polymorphism. The alleles were placed into three genotypes, <208/<208 bp, heterozygotes, and > or =208/> or =208 bp. A hierarchical ANOVA was performed with age of menarche as the dependent variable and LEP(1875) genotypes and maternal age (age of the mothers at birth of the subject) as independent variables. There was a significant (P or =30 years. If maternal age effects prove to be generalized, failure to take them into consideration could provide a source of hidden stratification that could significantly alter the replication of association studies.

Dietary intake and biochemical, hematologic, and immune status of vegans compared with nonvegetarians.

Dietary and nutritional status of individuals habitually consuming a vegan diet was evaluated by biochemical, hematologic, and immunologic measures in comparison with a nonvegetarian group. On the basis of 4-d dietary records, the intake of female and male vegans tended to be lower in fat, saturated fat, monounsaturated fat, and cholesterol and higher in dietary fiber than that of vegetarians. With computed food and supplement intakes, vegan diets provided significantly higher amounts of ascorbate, folate, magnesium, copper, and manganese in both female and male participants. The body mass index (BMI; in kg/m(2)) of the vegans was significantly lower than that of the nonvegetarians and 9 of the 25 vegans had a BMI <19. Serum ferritin concentrations were significantly lower in vegan men but iron and zinc status did not differ between the sexes. Mean serum vitamin B-12 and methylmalonic acid concentrations did not differ; however, 10 of the 25 vegans showed a vitamin B-12 deficit manifested by macrocytosis, circulating vitamin B-12 concentrations <150 pmol/L, or serum methylmalonic acid >376 nmol/L. Vegans had significantly lower leukocyte, lymphocyte, and platelet counts and lower concentrations of complement factor 3 and blood urea nitrogen but higher serum albumin concentrations. Vegans did not differ from nonvegetarians in functional immunocompetence assessed as mitogen stimulation or natural killer cell cytotoxic activity.

Association of the serotonin transporter gene with serum cholesterol levels and heart disease.

In a study of a group of elderly athletes we observed an unexpected association between serum cholesterol levels and the HTTLPR insertion/deletion polymorphism of the promoter region of the serotonin transporter gene (HTT, SLC6A4). As a follow-up we examined the potential association of this polymorphism with cholesterol and triglyceride levels, or heart disease, in two other groups of subjects. We examined the possible association between cholesterol levels and heart disease and genotypes of the HTTLPR insertion/deletion polymorphism of the promoter region of the HTT gene, in three independent study populations ranging from 42 to 90 years of age. For subjects 55 to 70 years of age in Group 1, cholesterol levels were significantly greater in the LS heterozygotes than either LL or SS homozygotes, indicating a heterosis effect (P 70 years of age. While these studies are preliminary and exploratory, they are consistent with a relationship of the HTT gene in cholesterol levels and a risk for heart disease. Replication of these findings in independent, epidemiologically based studies is required.

Early results of laparoscopic surgery for colorectal cancer. Retrospective analysis of 372 patients treated by Clinical Outcomes of Surgical Therapy (COST) Study Group.

UNLABELLED: This study was undertaken to determine the early experience of the embers of the COST Study Group with colorectal cancer treated by laparoscopic approaches. METHOD: A retrospective review was performed of all patients with colorectal cancer treated with laparoscopy by the COST Study Group before August 1994. Tumor site, stage, differentiation, procedure completion, presence of recurrence (local, distant, trocar site), and cause of death were analyzed. RESULTS: A total of 372 patients with adenocarcinoma of the colon and rectum were treated by laparoscopic approach between October 1991 and August 1994 (170 men and 192 women): right colectomy, 170; sigmoid colectomy, 55; low anterior resection, 56; abdominoperineal resection, 44; left colectomy, 22; colostomy, 8; total colectomy, 6; transverse colectomy, 7; exploration, 2. Conversion to an open procedure was required in 15.6 percent of cases. Operative mortality was 2 percent. Tumor characteristics were as follows: TNM state: I, 40 percent; II, 25 percent; III, 18 percent; IV, 17 percent; Differentiation: well-moderate, 88 percent; poor, 12 percent; carcinomatosis, 5 percent. Local (3.6 percent) and distant implantation occurred in four patients (1.1 percent). Only one of these patients died a cancer-related death (Stage III at 36 months). Cancer-related death rates increased with increasing stage of tumor: I, -4 percent; II, 17 percent; III, 31 percent; IV, 70 percent. CONCLUSION: A laparoscopic approach to colorectal cancer results in early outcome after treatment that is comparable with conventional therapy for colorectal cancer. A randomized trial is needed to compare long-term outcomes of open and laparoscopic approaches with colorectal cancer.

Genetic variants of the human obesity (OB) gene: association with body mass index in young women, psychiatric symptoms, and interaction with the dopamine D2 receptor (DRD2) gene.

To examine the possible role of genetic variants of the OB gene in obesity we examined alleles of a dinucleotide repeat polymorphism, D7S1875, close to the gene, in a group of adult, non-Hispanic Caucasians. There was a significant correlation with body mass index (BMI) at age 26-30 years for males and females combined (P = 0.04) and females only (P = 0.028). Because of the frequent association between obesity and psychiatric symptoms all subjects were screened with the Symptom List 90 (SCL-90). There was a significant increase in scores for anxiety (P = 0.0005), depression (P = 0.003), and other behaviors for subjects homozygous for the OB1875 < 208-bp alleles. Analysis of covariance indicated that this was directly related to the OB alleles and not secondary to the presence of obesity. There was a significant association between the BMI at ages 16 to 40 and homozygosity for the OB1875 < 208-bp alleles and/or the presence of the DRD2 Taq A1 allele for males and females combined (P = 0.002 to 0.005), and for females alone (P = 0.0017 to 0.0005). For females alone these two genes accounted for up to 22.8% of the variance of the BMI. These results are consistent with the polygenic inheritance of obesity, the greater involvement of genetic factors in women and younger individuals, and suggest that variants of the OB gene are causally involved not only in human obesity but its associated behavioral disorders.

Minimally invasive colectomy in elderly patients.

The safety of minimally invasive colectomy (laparoscopic or laparoscopically assisted colectomy) has not been evaluated in the elderly patient. Therefore, a prospective study of the outcome of minimally invasive colectomy (MIC) in patients aged 65 years or older was undertaken. Between October 1991 and September 1993, 103 elderly patients underwent attempted MIC (right colectomy, 53; left colectomy, sigmoid colectomy, or anterior resection, 36; abdominoperineal resection, 12; and total proctocolectomy with ileostomy, 2); 81 procedures were successfully completed. Complications occurred in 23% of patients converted to laparotomy (including one death) and in 25% undergoing successful MIC (two deaths, p = ns). The average length of postoperative stay was 5.3 days in the MIC group and 8.1 days for patients converted to laparotomy (p < 0.001). These results compare favorably with published results of traditional colectomy for elderly patients. We conclude that MIC is safe in the elderly patient and that further studies are warranted.

Minimally invasive colectomy: are the potential benefits realized?

Laparoscopic surgical techniques have recently been applied to various types of colon resection. Early reports have focused on the technical feasibility of these procedures, and it has not yet been clearly shown that such procedures benefit the patient. We reviewed our experience with 28 attempted minimally invasive colectomies (MICs) performed over a nine-month period. Laparoscopic or laparoscopic-assisted resections were successfully completed in 24 of these patients. We compared the results of surgery in these 24 patients with a group of 33 patients undergoing similar procedures at the same institution by the same surgeon in the nine months preceding the laparoscopic experience. The two groups of patients were similar with respect to age, weight, and the types of procedures performed. However, the postoperative length of stay for patients undergoing MIC (4.8 days) was significantly shorter than for those undergoing open colectomies (8.2 days). Patients undergoing MIC also regained bowel function significantly earlier than those undergoing open colectomy. The operative times for the minimally invasive procedures were significantly longer than for those undergoing open colectomy. No surgically related deaths were encountered, and morbidity was 13 percent. None of the four patients converted from laparoscopic to open colectomy suffered complications as a result of the attempted laparoscopic procedure. We conclude that MIC can be safely performed and does appear to reduce the duration of postoperative ileus and decrease the length of postoperative hospitalization.

Laparoscopic total proctocolectomy with creation of ileostomy for ulcerative colitis: report of two cases.

Laparoscopic techniques have recently been extended to the performance of segmental colon resections. We report two cases in which laparoscopic techniques were used to perform total proctocolectomy with ileostomy for patients with severe ulcerative colitis. Our experience encourages us that laparoscopic surgery will also prove to be of benefit for this subset of patients.

Anal sphincter reconstruction: anterior overlapping muscle repair.

Anal sphincter reconstruction for anal incontinence was performed in 55 women between 1973 and 1987 at The Jewish Hospital of St. Louis. The mean age was 34 years (range, 22-75 years). Incontinence was due to obstetric injury in 48 patients and to fistulotomy in 7 patients. Patients suffered from complete incontinence (41), incontinence of liquid stool and flatus (11), or incontinence of flatus only (3). All patients underwent an anterior overlapping sphincter muscle reconstruction, and one patient also had a posterior repair. Complete continence was restored in 28 patients, and partial continence was achieved in 24 patients. Only three patients remained totally incontinent. Clinical assessment did not accurately reflect functional outcome after 1 year of follow-up. No factor predicting outcome was found retrospectively. Clinical assessment of a patient's outcome may be inaccurate unless specific questions are asked. The use of a perineal drain reduced infection but did not affect outcome. Previous repair or associated rectovaginal fistula does not affect outcome. Sphincter injury owing to fistula disease may result in poor outcome after repair.

Multiple blood transfusions reduce the recurrence rate of Crohn's disease.

In order to determine whether perioperative blood transfusion affects the recurrence of Crohn's disease, the authors reviewed the records of 79 patients with Crohn's disease who underwent their initial intestinal resection at their institution. Recurrence of Crohn's disease was documented by radiographic studies, endoscopy, or laparotomy. During the hospital admission for resection, 45 patients received multiple red blood cell transfusions. Recurrence developed in 22 percent of these patients by 36 months, and the median time to recurrence was 35 months. In the 34 patients who did not receive multiple transfusions, recurrence was found in 44 percent by 36 months, and the median time to recurrence was 20 months. These differences are significant, using the Kaplan-Meier analysis (P less than 0.04). Recurrence in patients with disease limited to the small bowel or to the colon was not significantly affected by the transfusion status. However, recurrence developed in only 10 percent of multiply transfused patients with ileocolic disease by 36 months, whereas recurrence developed in 45 percent of the patients who were not multiply transfused. (Significance, P = 0.057). The authors believe that the observed decreased rate of recurrence of Crohn's disease in patients receiving multiple perioperative transfusions may represent another example of clinically significant immunosuppression from blood transfusion.

Peripheral vascular disease following radiation therapy.

Radiation therapy is effective for the treatment of many malignant diseases. This fact is well documented. The existence of complications in any treatment form does not obviate its usefulness. An awareness of possible complications, however, makes our treatment program more realistic and causes us to be more aware of the patient's complaints following therapy. One of our patients complained of claudication for seven years before an arteriogram was done. How many swollen, painful arms after mastectomy and irradiation have been passed off as due to lymphedema or a complaining patient? Exertional chest pain in a young person after mediastinal irradiation should not be overlooked. These symptomatic lesions are amenable to surgical correction. Great care must be spent when incising irradiated skin areas. The use of Silastic sheeting may be useful in extreme cases of radiation fibrosis involving the ureter. While no human studies are available for documentation, based on animal studies, it may be useful to decrease lipidemic situations through dietary prudence during radiation therapy. Finally, we are reminded again that many of our therapeutic triumphs are tarnished with serious side effects.

Pulmonary mechanics by spectral analysis of forced random noise.

The magnitude (Zrs) and phase angle (thetars) of the total respiratory impedance (Zrs), from 3 to 45 Hz, were rapidly obtained by a modification of the forced oscillation method, in which a random noise pressure wave is imposed on the respiratory system at the mouth and compared to the induced random flow using Fourier and spectral analysis. No significant amplitude or phase errors were introduced by the instrumentation. 10 normals, 5 smokers, and 5 patients with chronic obstructive lung disease (COPD) were studied. Measurements of Zrs were corrected for the parallel shunt impedance of the mouth, which was independently measured during a Valsalva maneuver, and from which the mechanical properties of the mouth were derived. There were small differences in Zrs between normals and smokers but both behaved approximately like a second-order system with thetars = 0 degree in the range of 5--9 Hz, and thetars in the range of +40 degrees at 20 Hz and +60 degrees at 40 Hz. In COPD, thetars remained more negative (compared to normals and smokers) at all frequencies and crossed 0 between 15 and 29 Hz. Changes in Zrs, similar in those in COPD, were also observed at low lung volumes in normals. These changes, the effects of a bronchodilator in COPD, and deviations of Zrs from second-order behavior in normals, can best be explained by a two-compartment parallel model, in which time-constant discrepancies between the lung parenchyma and compliant airway keep compliant greater than inertial reactance, resulting in a more negative phase angle as frequency is increased.