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© 2014.Background: We have combined functional gene polymorphisms with clinical factors to improve prediction and understanding of sporadic breast cancer risk, particularly within a high incidence Caucasian population. Methods: A polyfactorial risk model (

Dietary indoles, present in Brassica plants such as cabbage, broccoli, and Brussels sprouts, have been shown to provide potential protection against hormone-dependent cancers. 3,3'-Diindolylmethane (DIM) is under study as one of the main protective indole metabolites. Postmenopausal women aged 50-70 yr from Marin County, California, with a history of early-stage breast cancer, were screened for interest and eligibility in this pilot study on the effect of absorbable DIM (BioResponse-DIM) supplements on urinary hormone metabolites. The treatment group received daily DIM (108 mg DIM/day) supplements for 30 days, and the control group received a placebo capsule daily for 30 days. Urinary metabolite analysis included 2-hydroxyestrone (2-OHE1), 16-alpha hydroxyestrone (16alpha-OHE1), DIM, estrone (El), estradiol(E2), estriol (E3), 6beta-hydroxycortisol (6beta-OHC), and cortisol in the first morning urine sample before intervention and 31 days after intervention. Nineteen women completed the study,for a total of 10 in the treatment group and 9 in the placebo group. DIM-treated subjects, relative to placebo, showed a significant increase in levels of2-OHE1 (P=0. 020), DIM (P =0. 045), and cortisol (P = 0.039), and a nonsignificant increase of 47% in the 2-OHE1/16alpha-OHE1 ratio from 1.46 to 2.14 (P=0.059). In this pilot study, DIM increased the 2-hydroxylation of estrogen urinary metabolites. [ABSTRACT FROM AUTHOR]

We undertook this study to test whether progressive intervention would increase the use of mammography. In 1995, we randomly assigned into 2 groups 717 underserved women veterans in the Veterans Affairs Palo Alto (California) Health Care System (VAPAHCS) who earned less than $22,000 a year. The women were sent an informational letter and brochure explaining why mammography is needed and how often. The letter further requested that if the woman was due for a screening mammogram or if a lump or other recent change in her breast had occurred, that she call for scheduling of a free mammogram and a visit to the breast clinic. Women in group I (n = 351) received no further intervention. Women in group II (n = 366) received a follow-up phone call by a breast care nurse if they had not responded within 45 days of the informational mailing. The nurse talked to each woman about her particular needs, explained to her that the screening mammogram would be provided free of charge, and discussed transportation arrangements to the mammography facility. A total of 17 women in group I had mammograms versus 100 in group II during the same time period. We conclude that the additional intervention of a phone call by a breast care nurse increased use by more than 5-fold, which reached significance (P < .01). [ABSTRACT FROM AUTHOR]

Background: Myofascial pain that has been associated with cancer and increased risk of morbidity and mortality in cancer patients is intrinsically associated with low magnesium and low 25-hydroxyvitamin D (25(OH)D). Therefore, this physical finding was used as a clinical diagnostic proxy., Objective: The objective of this study was to assess the association and prevalence of disease in individuals with myofascial pain and low 25(OH)D in a county with low magnesium in the drinking water., Design: This is a retrospective cross-sectional study of a chart review of 269 subjects to assess subjects presenting with myofascial pain (assessed by tender trigger points) and 25(OH)D concentrations below 30 ng/mL or a history of 25(OH)D deficiency compared to those without these exposures., Results: The association between the exposure of low 25(OH)D levels and myofascial pain was compared to all cancers, colon polyps, and tendon ruptures. The odds of having cancer with the combined exposures was 10.14 times the odds of not having either exposure (95% confidence interval [CI], 5.08, 20.25, p < 0.001). For adenomatous colon polyps, the odds ratio (OR) was 7.24 (95% CI, 3.83, 13.69, p < 0.001), and for tendon rupture, the OR was 8.65 (95% CI, 3.76, 19.94, p < 0.001). Of 80 subjects who had both myofascial pain and 25(OH)D less than 30 ng/mL, 74 were tested for red blood cell (RBC) magnesium. Half of those subjects had RBC magnesium concentrations < 4.6 mg/dL, and 23% had levels below the reference range (4.0-6.4 mg/dL)., Conclusion: Myofascial pain as assessed by tender trigger points and 25(OH)D deficiency showed a significant association with cancer, adenomatous colon polyps, and tendon rupture. Further studies to verify these results are needed, especially in areas where there is low magnesium in the drinking water.

Background: We have combined functional gene polymorphisms with clinical factors to improve prediction and understanding of sporadic breast cancer risk, particularly within a high incidence Caucasian population., Methods: A polyfactorial risk model (PFRM) was built from both clinical data and functional single nucleotide polymorphism (SNP) gene candidates using multivariate logistic regression analysis on data from 5022 US Caucasian females (1671 breast cancer cases, 3351 controls), validated in an independent set of 1193 women (400 cases, 793 controls), and reassessed in a unique high incidence breast cancer population (165 cases, 173 controls) from Marin County, CA., Results: The optimized PFRM consisted of 22 SNPs (19 genes, 6 regulating steroid metabolism) and 5 clinical risk factors, and its 5-year and lifetime risk prediction performance proved significantly superior (~ 2-fold) over the Gail model (Breast Cancer Risk Assessment Tool, BCRAT), whether assessed by odds (OR) or positive likelihood (PLR) ratios over increasing model risk levels. Improved performance of the PFRM in high risk Marin women was due in part to genotype enrichment by a CYP11B2 (-344T/C) variant., Conclusions and General Significance: Since the optimized PFRM consistently outperformed BCRAT in all Caucasian study populations, it represents an improved personalized risk assessment tool. The finding of higher Marin County risk linked to a CYP11B2 aldosterone synthase SNP associated with essential hypertension offers a new genetic clue to sporadic breast cancer predisposition.

Background: Marin County, CA has very high incidence of breast cancer. Traditional risk factors, such as those included in the Gail model, do not effectively stratify breast cancer in this population. This retrospective case-control pilot study evaluates DNA from volunteers from a previous Marin County breast cancer epidemiology study. A polyfactorial risk model (OncoVue; InterGenetics Incorporated) that incorporates 22 polymorphisms in 19 genes and 5 clinical risk factors was used to stratify risk in Marin County women., Study Design: DNA genotyping was performed on 164 Caucasian women diagnosed with primary breast cancer in Marin County from 1997 to 1999 and 174 age- and ethnicity-matched control subjects. Individual lifetime risks were determined using the polyfactorial risk model and genotype frequencies in women at elevated risk were compared with the overall genotypes., Results: The vitamin D receptor VDR ApaI A2/A2 (rs7975232) homozygous polymorphism was present in high frequency in elevated-risk women. Sixty-four percent of elevated-risk women had the VDR Apa1 A2/A2 genotype compared with only 34% in the overall study, a statistically significant 1.9-fold difference (p = 0.0003). VDR Apa1 A2/a1 and a1/a1 genotypes were also present, but in lower frequencies., Conclusions: The high frequency of the VDR Apa1 A2/A2 homozygous polymorphism in women designated as elevated risk for breast cancer by the polyfactorial risk model might be related to the high incidence rates of breast cancer in Marin County, CA. Vitamin D supplementation could modify risk of breast cancer in this population., (Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Bladder injury is a complication of laparoscopic surgery with a reported incidence in the general surgery literature of 0.5% and in the gynecology literature of 2%. We describe how to recognize and treat the injury and how to avoid the problem., Case Reports: We report two cases of bladder injury repaired with a General Surgical Interventions (GSI) trocar and a balloon device used for laparoscopic extraperitoneal inguinal hernia repair. One patient had a prior appendectomy; the other had a prior midline incision from a suprapubic prostatectomy. We repaired the bladder injury, and the patients made a good recovery., Conclusion: When using the obturator and balloon device, it is important to stay anterior to the preperitoneal space and bladder. Prior lower abdominal surgery can be considered a relative contraindication to extraperitoneal laparoscopic hernia repair. Signs of gas in the Foley bag or hematuria should alert the surgeon to a bladder injury. A one- or two-layer repair of the bladder injury can be performed either laparoscopically or openly and is recommended for a visible injury. Mesh repair of the hernia can be completed provided no evidence exists of urinary tract infection. A Foley catheter is placed until healing occurs.

The Watanabe hereditary hyperlipidemic (WHHL) rabbit is an animal model that resembles humans with familial hyperlipidemia. In the thoracic aortae, there is also morphologic evidence of marked destruction of medial lamellar elastin fibers. Herein is provided the chemical evidence of elastolytic degradation. The levels of lysyl oxidase (L.Ox.), soluble elastin (SE) and insoluble elastin (IE) were estimated in thoracic aortae samples from New Zealand white (NZW) and WHHL rabbits at 6 months of age or 5 WHHL rabbits at 2.5 years of age. Enzyme-linked immunosorption assays (ELISA) were used in the L.Ox. and SE measurements. IE was measured following alkali extraction of aortae. There was a decrease in IE in thoracic aortae from Watanabe rabbits compared to NZW controls at 6 months of age (P < 0.1), and a further loss of IE in aortae from 2.5-year-old WHHL rabbits relative to the values at 6 months (P < 0.05). Average values for IE were: 130 mg/g for 6-month-old NZW, 100 mg/g for 6-month-old WHHL, and 60 mg/g for 2.5-year-old WHHL rabbits. Moreover, SE was only observed in aorta extracts from the older WHHL rabbits, a sign of elastolytic damage. There was also a five- to sixfold decrease in L.Ox. in the older vs. younger rabbits.

At age 3 years, WHHL rabbits are near the end of their lifespan, frequently dying from the progression of their hyperlipidemic disease from events such as myocardial infarction. Out of a colony of 20 three-year-old WHHL rabbits raised as part of a NIH breeding project, 2 rabbits actually died of a ruptured thoracic aortic aneurysm. The need for a model to study abdominal aortic aneurysm formation led us to explore further the abdominal aortic pathology in aged WHHL rabbits. Six rabbit abdominal aortas from 3-year-old WHHL rabbits were preserved in formalin, sectioned, and stained for elastin. These were compared to the same sections of six normolipidemic age matched New Zealand white (NZW) rabbits. There was significant (P less than or equal to .001) destruction of the medial lamellar elastin unit in the aorta of the WHHL rabbits compared with the control NZW rabbits. Severe cholesterol deposits appeared to destroy the medial lamellae from the inside out. No definite aneurysm formation was seen in the abdominal aorta despite the significant changes in the medial lamellar elastin units. Thus, this model could be used to study the elastin degeneration of the media, but not necessarily abdominal aortic aneurysm formation.

In the dog, alpha 1 adrenoceptors have been identified in the aorta, femoral mesenteric, and renal arteries. The concentration of alpha receptors may be regulated by hormones such as estrogen and progesterone and by drugs such as epinephrine. To assess whether sympathetic denervation, which is known to decrease norepinephrine output, might change the population of alpha 1 receptors in vascular smooth muscle, the femoral artery alpha 1 receptor population was examined 2 weeks after unilateral lumbar sympathectomy. [3H]Prazosin radioligand receptor assay analysis was used to measure the alpha 1 receptor populations. No statistical difference for dissociation constant and receptor density values between sympathectomy and nonsympathectomy femoral artery samples could be detected.

This study was designed to test the hypothesis that severe atherosclerosis changes aortic compliance. Compliance of a vessel is defined as change in volume per unit change in pressure and is a measure of the stiffness or distensibility of the vascular wall. Part of the energy delivered by the left ventricle in systole is used to propel the blood forward into the aorta and part of it to distend the aorta and major vessels. During diastole, the arterial walls recoil and provide energy for propulsion of blood, thereby making blood flow continuous. It is known that Watanabe hereditary hyperlipidemic rabbits develop severe atherosclerosis beginning at 6 months of age. Compliance of the ascending thoracic aorta was studied angiographically in eight Watanabe hereditary hyperlipidemic rabbits of ages greater than 6 months and six normal lipidemic New Zealand white rabbits of ages greater than 6 months, used as controls. The normal New Zealand white rabbits had an average blood cholesterol of 27.4 mg/dL, SD = 13.8, and a regional compliance in the ascending aorta of 0.004 mL/mm Hg, SD = 0.002, compared to the Watanabe hereditary hyperlipidemic rabbits with a cholesterol of 583.1 mg/dL, SD = 162.7, and a compliance of 0.0022 mL/mm Hg, SD = 0.0015. These are significant differences (p less than .05). In addition, the histopathology of the aorta of the Watanabe hyperlipidemic rabbit compared to that of the controls showed a significant decrease in the number of medial lamellar elastin units, an indicator of the decreased elasticity of the blood vessel wall.

Recent in vitro studies on isolated coronary and mesenteric arteries have shown that hyperlipidemia appears to hypersensitize the vascular arterial smooth muscle to drugs such as ergonovine and that this increased contractility seems to be mediated by a serotinergic mechanism. This results in vasospasm with exposure to certain vasoactive drugs such as serotonin or norepinephrine. However, in vivo quantification of this observed phenomenon has not been done. In the present study we used Watanabe hereditary hyperlipidemic (WHHL) rabbits (cholesterol level 459 +/- 216 mg/dL) and the normal lipidemic New Zealand white (NZW) rabbit (cholesterol level 35 +/- 19) as a control in the study of hyperlipidemia and blood flow changes in response to various vasoactive drugs. Blood flow measurements were made by the video dilution technique (VDT) following catheterization of the superior mesenteric artery. The serotinergic vasoactive drug ergonovine maleate was injected into the superior mesenteric artery at low dose (0.002) mg/kg) and high dose (0.004 mg/kg). A significant decrease (p less than .05) in blood flow was observed in response to high-dose ergonovine maleate in WHHL rabbits compared to the NZW rabbits. This in vivo experiment confirms the in vitro studies showing that hyperlipidemia sensitizes mesenteric arteries in the presence of serotinergic stimuli. The vasodilators verapamil hydrochloride and calcitonin gene-related peptide (CGRP) injected into the superior mesenteric artery caused a marked increase in flow in both the WHHL and the normal lipidemic NZW rabbits. This model can be used in the assessment of superior mesenteric artery ischemia and its reversal.

We developed a model that simulates distal arterial occlusive disease to determine the effects of sympathectomy on certain hemodynamic changes. Two groups of seven dogs each received unilateral distal popliteal artery ligation. Intra-arterial BPs, angiography, pulse volume recordings (PVRs), and photoplethysmograms were taken of the distal hind limb throughout the experiment. After ligation, PVR and distal hind limb pressures were lowered to less than half of the preligation values. Four days after unilateral distal popliteal artery ligation, group 2 dogs received lumbar sympathectomy on the same side as the ligation. One week after sympathectomy, the PVR amplitudes and pressures showed a transient significant rise. Two weeks after sympathectomy, the PVR pressures and amplitudes returned to the previous, diminished postligation values.

Since enhanced sensitivity to verapamil in essential hypertension has been noted, a relationship between verapamil and the sympathetic nervous system has been suggested. It has also been noted that both verapamil and lumbar sympathectomy appear to decrease the vasospasm seen in Raynaud's phenomenon. To further investigate the possible interrelationship between verapamil and the sympathetic nervous system, a unilateral lumbar sympathectomy was performed on eight dogs. Two weeks later the femoral artery blood flow response to intra-arterial verapamil was compared on the sympathectomy limb side and the non-sympathectomy limb side. Blood flow measurements were done without surgical trauma by video dilution technique. Although baseline femoral artery blood flow was unchanged and equal on both sides following sympathectomy (4.6% of cardiac output), there was a significant rise, p less than 0.05, in the blood flow response to verapamil on the side of sympathectomy. Therefore, sympathectomy appears to enhance the calcium channel blocking properties of verapamil.

The intent of this experiment was to study the postsynaptic vasoactive response to tolazoline hydrochloride and sodium-meglumine diatrizoate (Renografin-76) after a unilateral lumbar sympathectomy in a dog model. Both lower extremities were examined using the video dilution technique before and 1-2 weeks after unilateral lumbar sympathectomy (SE). Results showed (1) resting blood flow in the femoral artery as a percentage of cardiac output did not change after sympathectomy (mean and SD before and after SE: 7.0% +/- 2.3 and 6.0% +/- 2.9 respectively n = 13); (2) the reactive hyperemia in the femoral artery caused by sodium-meglumine diatrizoate (Renografin-76) was unchanged after sympathectomy; (3) the vasodilator effect of tolazoline hydrochloride decreased significantly after sympathectomy (p less than 0.05).

The need for health services, healthpower, and university participation is evident in Haiti, West Indies. The Hospital Albert Schweitzer in Haiti has a reputation for quality health care and a large volume of tropical disease that is worth experiencing. Health volunteers and university personnel are treated well and receive room and board in pleasant houses on the hospital complex. One becomes involved quite quickly in the active practice of medicine at the hospital and the necessity to read is facilitated by an excellent library. Reaching out to others and helping them achieve healthier lives is a direct form of hope for the future of the world. One can see that this makes a difference in one's own lifetime. To promote health for all it is important to promote changes in university training and research objectives that include interest in and concern for the scientific and educational problems associated with health for all. The Hospital Albert Schweitzer has always had these concerns and universities such as Yale have sent their surgical residents for one- to three-month rotations as part of their surgical training program. The residents are supervised by a board-certified general surgeon. Medical universities that participate in the global strategy of health for all could be allocated a greater number of residency training positions. To inquire further about the Hospital Albert Schweitzer write to Dr. Michel Jean-Baptiste, Medical Director, Hospital Albert Schweitzer, P.O.B. 1744, Port-Au-Prince, Haiti, West Indies.

In severe peripheral vascular disease, a patient may need not only an amputation but an axillary-femoral bypass. In order to prevent the potential problem of axillary-femoral graft compression by a prosthetic belt, the importance of amputation length is stressed in this case report discussion.