Search PubMed⌕ Search

Biomedical subjects

P Lavin

Publications and source records attributed to P Lavin.

At least 19 recordsLinked to original sources

Do women using hormone replacement treatment have less pre-existing cardiovascular risk.

BACKGROUND: Several studies have suggested that women who choose to use hormone replacement therapy (HRT) already, before starting this therapy, have a better cardiovascular risk profile than those who do not use it. Some of these studies contain factors of confusion and biases, such as HRT users' greater educational achievement or physical activity, which could have led to wrong conclusions. AIM: To study a cohort, without confounding factors in order to analyse whether the cardiovascular risk profile is different in women who choose to use HRT. MATERIAL AND METHODS: Coronary risk factors of 387 women between 45 and 64 were studied. This study was carried out at the Unit for the Preventive Medical Examination of the South Metropolitan Health Service in Santiago (Chile) during the annual check-up. The first evaluation was in 1991-1992; with a second evaluation 5 years later. Of all the women, 174 (45%) never received hormones (Group A), 124 (32%) were HRT users at the time (Group B), and 89 (23%) were former-users (Group C). RESULTS: No differences were found between the three groups for age, body mass index (BMI), educational background, alcohol consumption, smoking or physical activity. Blood pressure was similar in the three groups. No significant differences were found in total cholesterol (A, 221.7+/-42.2; B, 228.2+/-47.0; and C, 227.3+/-44.9 mg/dl); high density lipoprotein (HDL, A, 53.5+/-13.2; B, 51.8+/-12.8; and C, 54.0+/-12.4 mg/dl); low density lipoprotein (LDL, A, 141.7+/-38.9; B, 148.5+/-43.1 and C, 148.3+/-43.8 mg/dl); triglycerides (A, 134.5+/-67.9; B, 141.0+/-66.1; and C, 127.3+/-68.5 mg/dl) and glucose plasma levels (A, 90.5+/-32.2; B, 87.7+/-15.3; and C, 85.0+/-8.8 mg/dl). CONCLUSIONS: Our results suggest that women who choose to use HRT have a cardiovascular risk profile, before starting the therapy, similar to those who do not use it.

Blood Glucose↗

Body size at birth and blood pressure among children in developing countries.

BACKGROUND: Studies in developed countries have shown that reduced fetal growth is related to raised blood pressure in childhood and adult life. Little is known about this association in developing countries, where fetal growth retardation is common. METHODS: In 1994-1995, we measured blood pressure in 1570 3-6-year-old children living in China, Guatemala, Chile, Nigeria and Sweden. We related their blood pressure to patterns of fetal growth, as measured by body proportions at birth. The children were all born after 37 weeks gestation and weighed more than 2.5 kg at birth. RESULTS: In each country, blood pressure was positively related to the child's current weight. After adjusting for this and gender, systolic pressure was inversely related to size at birth in all countries except Nigeria. In Chile, China and Guatemala, children who were proportionately small at birth had raised systolic pressure. For example, in Chile, systolic pressure adjusted for current weight increased by 4.9 mmHg (95% CI : 2.1, 7.7) for every kilogram decrease in birthweight, by 1 mmHg (95% CI : 0.4, 1.6) for every centimetre decrease in birth length, and by 1.3 mmHg (95% CI : 0.4, 2.2) for every centimetre decrease in head circumference at birth. In Sweden, systolic pressure was higher in children who were disproportionately small, that is thin, at birth. Systolic pressure increased by 0.3 mmHg (95% CI : 0.0, 0.6) for every unit (kg/m3) decrease in ponderal index at birth. These associations were independent of the duration of gestation. CONCLUSIONS: Raised blood pressure among children in three samples from China, Central and South America is related to proportionate reduction in body size at birth, which results from reduced growth throughout gestation. The relation between fetal growth and blood pressure may be different in African populations. Proportionately reduced fetal growth is the prevalent pattern of fetal growth retardation in developing countries, and is associated with chronic undernutrition among women. Improvement in the nutrition and health of girls and young women may be important in preventing cardiovascular disease in developing countries.

Birth Weight↗

Anterior ischemic optic neuropathy: a complication after systemic inflammatory response syndrome.

BACKGROUND: Patients are surviving previously fatal injuries. Unique morbidities are occurring in these survivors. Anterior ischemic optic neuropathy represents a previously unrecognized cause of blindness in the trauma victim. We hypothesize that this phenomenon is caused by unique characteristics of optic edema/ pressure or decreased blood flow associated with massive resuscitation. METHODS: Between November of 1991 and August of 1998, there were 18,199 admissions to our trauma center. Of this group, 350 patients required massive volume resuscitation (>20 liters infused over first 24 hours). Patients having closed head injuries, facial fractures or direct orbital trauma were excluded from study. The following variables were studied: demographics, injury severity (Injury Severity Score, highest lactate, worst base deficit, and lowest pH) crystalloid and transfusion requirements, ventilator requirements (PEEP) RESULTS: Of the 350 patients with massive resuscitation, 9 patients were diagnosed with anterior ischemic optic neuropathy (2.6%). Of these, seven patients required celiotomy (78%). Six of the seven celiotomy patients had damage control celiotomies and abdominal compartment syndrome (86%). One patient had a repair of a subclavian artery; one had a complex acetabular repair. Blindness was unilateral in five patients and bilateral in four. All nine patients had evidence of global hypoperfusion, systemic inflammatory response, massive resuscitation, and high ventilatory support; one patient required cardiopulmonary resuscitation. CONCLUSION: Prone positioning is known to be associated with an increased intraocular pressure. We postulate that the combination of massive resuscitation and prone positioning will increase the incidence of anterior ischemic optic neuropathy. As such, we recommend that prone positioning for adult respiratory distress syndrome be reserved for only those patients at risk of death.

Adolescent↗

Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis.

OBJECTIVE: To evaluate RA-1, a standardized plant extract formulation, traditionally considered a safe, effective antiarthritic in the Asian-Indian Ayurvedic medicinal system. METHODS: One hundred eighty-two patients with active-on-chronic rheumatoid arthritis (RA) participated in a 16 week randomized, double blind, placebo controlled, parallel efficacy clinical drug trial in Pune, India. Tenderness, pain, swelling, and several other efficacy measures were assessed by (1) ACR core set 20% and 50% improvement; (2) ACR 20% improvement response. An intent-to-treat analysis was performed; p<0.05 considered significant. RESULTS: Seventeen patients withdrew (active = 9; placebo = 8); none withdrew due to drug toxicity. An unprecedented placebo response (often p<0.001 in within-group change) was observed. The active RA-1 group remained numerically superior at all evaluation timepoints. RA-1 demonstrated few significant differences: (1) increased proportion with 50% reduction in swollen joint count (95% CI approximately 1.52, 29.90) and swollen joint score (95% CI approximately 0.91, 28.73); (2) reduced rheumatoid factor (95% CI approximately -303.7, -2.72); 39% in the RA-1 group versus 30% placebo showed ACR 20% improvement (95% CI approximately -5.48, 24.59). Only minor side effects were seen, with no significant differences by treatment group. CONCLUSION: In a trial with sufficient power, RA-1 revealed efficacy that was not significantly superior to the strong placebo response, except for improvement in joint swelling. Further, the effect on RF and good safety profile led to an open label phase.

Acetaminophen↗

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Adolescent↗

Incidence and predictors of cervical dysplasia in patients with minimally abnormal Papanicolaou smears.

OBJECTIVE: To estimate the incidence of dysplasia in patients with Papanicolaou smears showing atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (SIL) and to identify clinical predictors of dysplasia in these patients. METHODS: Patients referred for ASCUS and low-grade SIL were reviewed retrospectively. All patients were evaluated with immediate colposcopy. A multivariate logistic regression analysis was performed to identify clinical predictors of histologic SIL and histologic high-grade SIL. RESULTS: One hundred thirty-seven (34%) of 406 consecutive patients had histologic SIL. Regression analysis identified age (under 35 versus 35 years or above) and initial smear (low-grade SIL versus ASCUS) as statistically significant predictors of histologic SIL and high-grade SIL (P < .001). When patient outcomes were analyzed by age and initial Papanicolaou smear results, the subgroup of patients 35 years or older with ASCUS had low incidences of histologic SIL (14%) and high-grade SIL (1%). The other subgroups (under 35 years with ASCUS, under 35 years with low-grade SIL, and 35 years or older with low-grade SIL) had incidences of histologic SIL and histologic high-grade SIL of at least 28% and 14%, respectively. CONCLUSION: The high incidence of dysplasia in patients with minimally abnormal Papanicolaou smears suggests that immediate colposcopy might be appropriate for many of these patients. Age and initial Papanicolaou smear are predictive of dysplasia and might be used to select patients who have low incidence of dysplasia and might not require immediate colposcopy.

Adult↗

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Carcinoembryonic Antigen↗

The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas.

Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospective series of 202 patients with stage T1a,b invasive breast carcinomas was evaluated. The clinicopathological features (age, histological grade, extensive in situ carcinoma, hormone receptor status, and nodal metastasis) as well as microvessel density and the expression of c-erb-B2, p53, MIB-1/Ki-67, and cdc25B were assessed. In addition, expression of the cell cycle inhibitor p27 was evaluated. Nineteen patients (18% of patients who had axillary dissection) had locoregional lymph node metastases. Forty-two % of them died of disease (median survival, 112 months), whereas mortality was 11% in node-negative patients (median survival, 168 months; P = 0.0055). Patients with low p27 expression had a median survival of 139 months (17% mortality) versus 174 months (9% mortality) in the group with high p27 expression (P = 0.0233). Lack of p27 was associated with poor prognosis when node-positive patients were excluded (P = 0.0252). Nodal status and low p27 were found to be the only independent prognostic parameters by both univariate and multivariate analysis, with relative risks of dying of disease of 4.9 (P = 0.001) and 3.4 (P = 0.0306), respectively. Assessment of p27, which yields prognostic information in node-negative patients, could be useful to identify patients with small, invasive breast carcinomas who might benefit from adjuvant therapy.

Age Factors↗

Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas.

The cell-cycle inhibitor p27 is a potential tumor suppressor, but its gene has never been found inactivated in human tumors. Because cell-cycle regulation of p27 cellular abundance occurs at the post-transcriptional level, we analyzed p27 protein expression and degradation in human colorectal carcinomas. Proteasome-mediated degradation activity of p27 was compared with its protein levels in a subset of tumor samples. We found that carcinomas with low or absent p27 protein displayed enhanced proteolytic activity specific for p27, suggesting that low p27 expression can result from increased proteasome-mediated degradation rather than altered gene expression. Patients whose tumors expressed p27 had a median survival of 151 months, whereas patients who lacked p27 (10%) had a median survival of 69 months. By multivariate analysis, p27 was found to be an independent prognostic marker. Lack of p27 was associated with poor prognosis (2.9 risk ratio for death; P = 0.003). The absence of p27 protein expression is thus a powerful negative prognostic marker in colorectal carcinomas, particularly in stage II tumors, and thereby may help in the selection of patients who will benefit from adjuvant therapy. These data suggest that aggressive tumors may result from the selection of a clone or clones that lack p27 due to increased proteasome-mediated degradation.

Adenocarcinoma↗

The DCC protein and prognosis in colorectal cancer.

BACKGROUND: Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma. METHODS: The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy. RESULTS: The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03). CONCLUSIONS: DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients.

Aged↗

Enlarged extraocular muscles from metastatic signet ring carcinoma.

Enlarged extraocular muscles usually occur from inflammatory conditions, but in rare instances metastatic tumors that invade the muscles will require a biopsy and specific treatment. The authors report what they believe to be the third case of metastases to the extraocular muscles from signet ring cell adenocarcinoma of an unknown primary site.

Antineoplastic Agents↗

Effect of neurovestibular stimulation on autonomic regulation.

Conditions associated with nausea and vomiting, such as motion sickness or side effects of medications, are commonly associated with a clinical picture consistent with parasympathetic activation and sympathetic withdrawal. It can be postulated, therefore, that vestibular stimulation contributes to sympathetic withdrawal. To test this hypothesis five normal volunteers, 24-33 years old, were studied during caloric vestibular stimulation while monitoring muscle sympathetic nerve activity directly through a needle electrode placed in a peroneal nerve. The ear was irrigated with water at a flow rate of 450 ml/min and 37 degrees C. The water temperature was sequentially lowered by 7 degree C intervals until intolerable side effects developed or a temperature of 16 degrees C was reached. Nystagmus was induced in all subjects, but heart rate, blood pressure, muscle sympathetic nerve activity and plasma norepinephrine levels did not change significantly during or after caloric stimulation, even when the subjects felt dizzy and nauseated. No evidence of sympathetic withdrawal was observed in any subject either by muscle sympathetic nerve activity or plasma norepinephrine measurements. In conclusion, we have found that selective vestibular stimulation is not accompanied by significant changes in the sympathetic nervous system function. In particular, no sympathetic withdrawal was observed. It could be argued that lack of sympathetic stimulation is an inadequate response to the symptoms associated with caloric stimulation.

Adult↗

Decrease of optic disc cupping and pallor of ocular hypertensives with timolol therapy.

PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on optic disc cupping and pallor in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to placebo or 0.5% timolol drops to both eyes in a double masked clinical trial. Measurements of ocular pressure and photographs of the optic disc for cupping by photogrammetry and pallor by computerized image analysis were made at about 3 month intervals, for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol developed a significant decrease in ocular pressure and a significant decrease in optic disc cupping with a smaller decrease in pallor compared to subject treated with placebo. Multivariate analyses indicated that the decrease of optic disc cupping and pallor was not associated with the ocular pressure on treatment or the decrease in ocular pressure during the trial. CONCLUSION: Timolol treatment was associated with a decrease in optic disc cupping and pallor. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure.

Double-Blind Method↗

Increase of retinal nerve fiber layer thickness in ocular hypertensives with timolol therapy.

PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on retinal nerve fiber layer thickness in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to receive placebo or 0.5% timolol drops to both eyes for 18 to 24 months in a double masked clinical trial. Measurements of ocular pressure and photographs of retinal nerve fiber layer using stereophotogrammetric techniques were made at about 3 month intervals for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with timolol had a significant decrease in ocular pressure and developed a significant increase in retinal nerve fiber layer thickness compared to subjects treated with placebo. Multivariate analyses indicated that the increase of retinal nerve layer thickness was not associated either with the ocular pressure on treatment or the decrease in ocular pressure on treatment. CONCLUSION: Timolol treatment was associated with an increase of retinal nerve fiber thickness. The effect of timolol appears to be related to mechanisms other than the decrease in ocular pressure.

Double-Blind Method↗

Increase of retinal vessel width in ocular hypertensives with timolol therapy.

PURPOSE: The purpose of this study was to determine whether timolol drops compared to placebo drops had a significant effect on retinal vessel width in ocular hypertensives. METHODS: Thirty-seven ocular hypertensives were randomly assigned to receive placebo or 0.5% timolol drops to both eyes for 18 to 24 months in a double masked clinical trial. Measurements of ocular pressure and retinal vessel width by computerized image analysis from fundus photographs were made at about 3 month intervals for 18 to 24 months of follow-up. RESULTS: None of the subjects developed visual field loss when tested with the Goldmann perimeter by kinetic and static means at six month intervals. Subjects treated with the placebo showed no change in ocular pressure and a significant decrease in retinal vessel width over time especially in the right eye. Subjects treated with timolol had an increase in retinal vessel width compared to the placebo group significant especially for the superior temporal vein. Multivariate analyses indicated that the increase of retinal vessel width was not associated mainly with the ocular pressure on treatment or decrease in ocular pressure on treatment. CONCLUSION: Timolol treatment was associated with an increase of retinal vessel width. The effect of timolol appears to be related primarily to mechanisms other than the decrease in ocular pressure.

Double-Blind Method↗

Shifting proportions of gastric adenocarcinomas.

OBJECTIVES: To substantiate reports of increasing proportions of gastric adenocarcinoma of diffuse histologic type and in the proximal portion of the stomach, to better understand the prognostic features that govern survival, and to determine whether alterations of operative strategy might improve the surgical results. DESIGN: Retrospective analysis of 289 consecutive patients with gastric adenocarcinoma operated on by general surgeons over a 26-year period. Records were reviewed for location, histologic type, resection, operative mortality, lymph node status, and outcome. SETTING: The Section of Surgical Oncology, the New England Deaconess Hospital, Boston, Mass. MAIN OUTCOME MEASURES: Survival rate, length of life of the patients who died, and operative mortality. RESULTS: A marked and significant shift of gastric adenocarcinoma to a proximal location (54% between 1985 and 1990) occurred over 26 years (P = .0075) with a significant stage improvement at presentation (P = .0235). Percentages of cancers that were of the diffuse, poorly differentiated histologic type increased to 48%. More curative operations were performed in the last period (61%), and this upward trend from 37% was significant. Proximal gastric cancers had a poorer prognosis with more operative deaths, more lymph node metastases, and worse survival rates than distal cancers. Poor survival rates occurred even when comparing patients with negative lymph nodes or favorable histologic features with patients with similar distal cancers. CONCLUSIONS: Despite significant increases in the proportion of proximal cancers, survival rates have improved only slightly. Nodal status plays a less prognostic role than does location or histologic type but does provide prognostic information for individual locations. Survival rates for diffuse histologic cancer were consistently worse than those for intestinal histologic cancer, which emphasizes the underlying disease biology controlling outcome. Radical lymphadenectomy for gastric adenocarcinoma would not improve surgical outcome in the United States.

Actuarial Analysis↗