Pulsatile blood flow in a stenosed artery—a theoretical model

To understand the special flow conditions which may be produced by the presence of stenosis in arteries, an analytical solution is obtained for pulsatile laminar flow in an elliptic tube. Blood is approximated by a Newtonian model and the geometry of the stenosis is introduced by specifying the change in area of cross-section of the stenosed artery with axial distance. The results for velocity, pressure, shear stress and impedance are presented. These are compared with the steady flow results as well as with those of the flow in a stenosed tube of circular cross-section. The study indicates that the fluid dynamic characteristics of the flow are affected by the percentage of stenosis as well as the geometry of the stenosis. The frequency of oscillation is also found to influence shearing stress and the impedance.     

Prevalence of diabetic complications in fibrocalculous pancreatic diabetic patients and type 2 diabetic patients: a cross-sectional comparative study

OBJECTIVE: To determine the prevalence of diabetes-related complications in subjects with fibrocalculous pancreatic diabetes (FCPD) and compare them with subjects with type 2 diabetes mellitus matched for age, sex, and duration of diabetes. METHODS: The study group comprised of 277 FCPD patients and 277 age, sex, and duration of diabetes-matched type 2 diabetic patients. All the study subjects underwent a detailed clinical examination, and fasting blood samples were obtained for biochemical studies. Peripheral Doppler was used for diagnosis of peripheral vascular disease (PVD). Vibratory perception threshold (VPT) was determined using biothesiometry for diagnosis of neuropathy. Diagnosis of coronary artery disease (CAD) was based on medical history and 12-lead resting ECG. Retinal photographs were used for diagnosis of retinopathy using a modified version of Early Treatment Diabetic Retinopathy Study (ETDRS) grading system. RESULTS: FCPD patients had lower body mass index (BMI) (P<.001), systolic blood pressure (P<.0001), diastolic blood pressure (P<.001), serum cholesterol (P<.001), serum triglyceride (P<.001), and serum creatinine (P<.01) but higher glycosylated hemoglobin (P<.001) levels compared to patients with type 2 diabetes. Prevalence of CAD was significantly higher among type 2 diabetic patients (11.9%) compared to FCPD patients (5.1%), P<.003. There was no significant difference in the prevalence of other diabetic complications between the two study groups (type 2 diabetes vs. FCPD: retinopathy-37.2% vs. 30.1%, PVD-4.3% vs. 4.7%, Neuropathy-25.3% vs. 20.9%, Nephropathy-15.0% vs. 10.1%). Multiple logistic regression analysis revealed the following risk factors for diabetes complications among type 2 diabetic subjects-retinopathy: BMI (P=.028), duration of diabetes (P<.001), and glycosylated hemoglobin (P=.026); nephropathy: diastolic blood pressure (P=.016) and glycosylated hemoglobin (P=.040); neuropathy: age (P<.001), duration of diabetes (P=.003), and glycosylated hemoglobin (P=.001). Among subjects with FCPD, systolic blood pressure (P=.013), glycosylated hemoglobin (P=.021), and duration of diabetes (P<.001) were associated with retinopathy; BMI (P=.057), glycosylated hemoglobin (P=.010), and duration of diabetes (P=.024) with nephropathy and age (P=.011) and BMI (P=.010) with neuropathy. Conclusion: The prevalence of retinopathy, nephropathy, neuropathy, and PVD was similar among FCPD patients and type 2 diabetic patients, but the prevalence of CAD was lower among FCPD patients.     

Developmental programming: differential effects of prenatal exposure to bisphenol-A or methoxychlor on reproductive function

Increased occurrence of reproductive disorders has raised concerns regarding the impact of endocrine-disrupting chemicals on reproductive health, especially when such exposure occurs during fetal life. Prenatal testosterone (T) treatment leads to growth retardation, postnatal hypergonadotropism, compromised estradiol-positive feedback, polycystic ovaries, and infertility in the adult. Prenatal dihydrotestosterone treatment failed to affect ovarian morphology or estradiol-positive feedback, suggesting that effects of prenatal T may be facilitated via conversion of T to estradiol, thus raising concerns regarding fetal exposure to estrogenic endocrine-disrupting chemicals. This study tested whether fetal exposure to methoxychlor (MXC) or bisphenol A (BPA) would disrupt cyclicity in the ewe. Suffolk ewes were administered MXC (n=10), BPA (n=10) (5 mg/kg.d sc in cotton seed oil) or the vehicle (C; n=16) from d 30 to 90 of gestation. On d 60 of treatment, maternal MXC concentrations in fat tissue and BPA in blood averaged approximately 200 microg/g fat and 37.4+/-3.3 ng/ml, respectively. Birth weights of BPA offspring were lower (P<0.05) relative to C. There was no difference in the time of puberty between groups. BPA females were hypergonadotropic during early postnatal life and ended their breeding season later, compared with C. Characterization of cyclic changes after synchronization with prostaglandin F2alpha in five C, six MXC, and six BPA females found that the onset of the LH surge was delayed in MXC (P<0.05) and the LH surge magnitude severely dampened (P<0.05) in BPA sheep. These findings suggest that prenatal BPA and MXC exposure have long-term differential effects on a variety of reproductive endocrine parameters that could impact fertility.     

Developmental programming: gestational testosterone treatment alters fetal ovarian gene expression

Prenatal testosterone (T) treatment leads to polycystic ovarian morphology, enhanced follicular recruitment/depletion, and increased estradiol secretion. This study addresses whether expression of key ovarian genes and microRNA are altered by prenatal T excess and whether changes are mediated by androgenic or estrogenic actions of T. Pregnant Suffolk ewes were treated with T or T plus the androgen receptor antagonist, flutamide (T+F) from d 30 to 90 of gestation. Expression of steroidogenic enzymes, steroid/gonadotropin receptors, and key ovarian regulators were measured by RT-PCR using RNA obtained from fetal ovaries collected on d 65 [n = 4, 5, and 5 for T, T+F, and control groups, respectively] and d 90 (n = 5, 7, 4) of gestation. Additionally, fetal d 90 RNA were hybridized to multispecies microRNA microarrays. Prenatal T decreased (P < 0.05) Cyp11a1 expression (3.7-fold) in d 90 ovaries and increased Cyp19 (3.9-fold) and 5α-reductase (1.8-fold) expression in d 65 ovaries. Flutamide prevented the T-induced decrease in Cyp11a1 mRNA at d 90 but not the Cyp19 and 5α-reductase increase in d 65 ovaries. Cotreatment with T+F increased Cyp11a1 (3.0-fold) expression in d 65 ovaries, relative to control and T-treated ovaries. Prenatal T altered fetal ovarian microRNA expression, including miR-497 and miR-15b, members of the same family that have been implicated in insulin signaling. These studies demonstrate that maternal T treatment alters fetal ovarian steroidogenic gene and microRNA expression and implicate direct actions of estrogens in addition to androgens in the reprogramming of ovarian developmental trajectory leading up to adult reproductive pathologies.     

Abdominal colon and rectal operations in the elderly

Sixty-seven abdominal operations for colon and rectal disorders were performed on 56 patients 80 years of age or older from January 1, 1984 to June 30, 1989. Nine patients required multiple operations. Sixty-two procedures (92 percent) were performed on patients in their ninth decade; two operations were performed on patients 95 years of age or older. Forty-five patients (80 percent) were operated upon for carcinoma. Operations included segmental colectomy (33 patients), low anterior resection (12 patients), total abdominal colectomy (3 patients) and abdominoperineal resection (2 patients). Forty patients were classified as ASA Class III; the majority were monitored in the surgical intensive care unit for a mean of 2.84 days. Thirty patients were monitored with arterial catheters and 21 with central invasive monitoring. Operative mortality was 7 percent (4 patients). Two patients died from diffuse carcinomatosis; one patient had a fatal myocardial infarction. The final death occurred from multisystem organ failure following anastomotic dehiscence. Twenty-seven operations were performed without postoperative complications; 18 operations were followed by a single minor complication. The average hospital stay was 18.96 days. All patients were admitted from home. Thirty-three returned home postoperatively; 16 were discharged to an extended care facility. In conclusion, elderly patients with colon and rectal disorders can be operated upon with acceptable morbidity and mortality. Age alone should not interdict surgical therapy.     

Surgical treatment of low rectovaginal fistulas

Forty women with low rectovaginal fistulas were operated upon over a 9-year period. The etiology of the fistula in the majority was obstetric. Nine women had prior attempts to repair the fistula. All 40 women were managed with endorectal advancement flap with the addition of sphincteroplasty or perineal body reconstruction in 15 patients and rectocele repair in six patients. Postoperative complications included urinary difficulties (two patients) and wound complications (three patients). There were two recurrences. All women treated with sphincteroplasty or perineal body reconstruction were continent. Seven women complained of varying degrees of incontinence postoperatively; none had undergone sphincter or perineal body reconstruction. Endorectal advancement flap is a safe and effective operation for women with rectovaginal fistulas. Concomitant sphincteroplasty or perineal body reconstruction should be performed in women with historical, physical, or manometric evidence of incontinence.     

Development of an immunological staging system to prognosticate disease course in malignant cervical neoplasia

A multiparameter analysis of immune function was done on patients with squamous cell carcinoma of the uterine cervix to look for any variable(s) that could be correlated with the clinical stage of the disease. Five immunological variables, viz., CD4+ lymphocytes, CD4/CD8 ratio, natural killer cells, concanavalin A-induced suppressor index, and circulating immune complexes, were found to consistently vary with tumor load. When these variables were subjected to a multiple regression and multivariate analysis, an equation for a diagnostic index curve was derived. Application of this equation led to an immunological staging system which could be used as an excellent prognostic indicator. The immunological staging system showed that patients classified into a particular clinical (FIGO) stage behaved in a heterogeneous way immunologically and that patients developing recurrent disease could easily be identified from those remaining disease free, even before treatment. Subsequent follow-up of these patients further confirmed this observation, with the recurrent disease group easily identifiable. These results point out the immense potential of such a staging system and the importance of immunological evaluation in the preliminary management of patients with malignant cervical neoplasia.     

Intra-follicular activin availability is altered in prenatally-androgenized lambs.

Prenatal exposure of sheep to testosterone (T) disrupts ovarian cyclicity and leads to anovulation in adulthood. We propose that the disruption of ovarian function in prenatally-androgenized sheep is mediated via follicular defects stemming from reduced intrafollicular activin availability/action. The intra-follicular activin availability/action that facilitates follicular development is dictated by the relative proportions of activins, inhibins (antagonists of activin action) and follistatins (FS; binding proteins of activin and negator of activin action). Inhibin alpha, beta A, beta B, and FS mRNA expression were determined by in situ hybridization in 5 week-old ovaries from control (C) lambs or those exposed to testosterone (T) or DHT from 30-90 days of gestation. In utero exposure to T, but not DHT, increased total ovarian weight (0.4+/-0.1,1.5+/-0.5 and 0.3+/-0.1 g, C, T and DHT, respectively) and total number of follicles (16.5+/-2.8,37.8+/-7.9, and 18.8+/-3.0). With the exception of two follicles in T animals, all follicles were < or = 2 mm in diameter. All follicles < or = 2 mm in all groups expressed FSH receptor mRNA in the granulosa cells and LH receptor only in the thecal cells. The percentage of follicles expressing FS mRNA was increased (P<0.05) in sheep prenatally-androgenized with either T (80.4+/-8) or DHT (80.3+/-5.5) as compared to C (50.8+/-8.2). In contrast, the percentage of follicles expressing activin beta B mRNA tended to be lower (P=0.06) in the T (30.9+/-7.1) and DHT (40.5+/-3.3) groups as compared to C (66.1+/-15.6). Increased expression of FS along with the reduced expression of activin beta B mRNA provides evidence for compromised intra-follicular activin availability in the majority of follicles in the androgenized groups. The increase in ovarian weight and follicular number in the T, but not in the DHT group, suggests that the effects of T are mediated through the action of estrogen. We speculate that the decrease in relative abundance of activin may contribute to the selection defects in prenatally-androgenized sheep. If true, this may be a useful model to understand the etiology of polycystic ovarian syndrome.