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Biomedical subjects

C R Gross

Publications and source records attributed to C R Gross.

At least 37 records · Page 2Linked to original sources

Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3'-flanking region.

Genetic differences in the metabolism of carcinogens may codetermine individual predisposition to cancer. Cytochrome P-4501A1 (CYP1A1) metabolically activates precarcinogens in cigarette smoke, such as benzo(a)pyrene, which is also an inducer of CYP1A1. Two point mutations have been reported, m1 in the 3'-flanking region (6235T to C), and m2 within exon 7 (4889A to G), the latter leading to an isoleucine to valine exchange. In the Japanese population m1 and m2 are correlated with lung cancer, suggesting an increased susceptibility to cigarette smoking related lung cancer. We studied 142 lung cancer and 171 reference patients in an ethnically homogeneous German group for m1 and m2 mutations by restriction fragment length polymorphism and allele-specific polymerase chain reaction, respectively. No statistically significant difference was found in the distribution of m1 alleles between lung cancer and controls; the frequency was 8.5% and 7.3% of the alleles, respectively (odds ratio = 1.17). A trend to an overrepresentation of m1 alleles was observed among 52 squamous cell carcinoma patients (odds ratio = 1.65). In contrast, the frequency of m2 alleles in lung cancer patients was twofold higher (6.7%) than in the reference group (3.2%; odds ratio = 2.16; 95% confidence limits 0.96-5.11, P = 0.033); the odds ratio of m2 alleles in squamous cell carcinoma was 2.51 (95% confidence limits 0.85-7.05, P = 0.05). There was a close genetic linkage of m2 to m1 (10 of 11 reference patients), but a significantly higher number of cancer patients showed no linkage compared to the controls (odds ratio = 8.89, 95% confidence limits 0.83-433, P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pulmonary function after successful heart transplantation. One year follow-up.

Congestive heart failure (CHF) has been associated with the development of restrictive ventilatory abnormalities and decreased pulmonary diffusing capacity. Whether these physiologic changes reflect permanent alterations of lung anatomy or result solely from potentially reversible alterations of lung water is not known. To examine this issue, we reviewed the pulmonary function tests (PFTs) and cardiac catheterization data from recipients of successful heart transplants prior to and 1 year after transplantation. Thirty-eight patients met the inclusion criteria (median age, 52 years). The median duration of symptomatic CHF prior to transplantation was 22 months (range, 3 to 72 months). After transplantation, spirometry revealed an improvement in FEV1 from 75.8 +/- 3.5 to 99.1 +/- 2.8 percent of predicted and FVC from 81.3 +/- 3.7 to 101.6 +/- 3.0 percent of predicted (p < 0.001). The FEV1/FVC ratio remained unchanged at 80 percent. Nonsmokers and former smokers had similar improvements in spirometry after transplantation. The TLC improved from 91.1 +/- 3.3 to 105.5 +/- 2.9 percent of predicted (p < 0.001); this improvement was due to an increase in inspiratory capacity. Diffusing capacity for carbon monoxide was decreased before transplantation and showed a small decline after transplantation from 82.3 +/- 3.2 to 76.8 +/- 2.6 percent of predicted (p < 0.05). After correction of severe CHF by cardiac transplantation, normalization of FEV1, FVC, and TLC can be anticipated. Diffusing capacity, however, may actually decline after transplantation.

Adolescent↗

Health-related quality of life outcomes of pancreas transplant recipients.

The health status and quality of life outcomes of 131 patients who were 1 to 11 years post-pancreas transplant were studied. Patients were compared based on the current status of their pancreas graft, i.e. whether or not their grafts were successful in maintaining an insulin-independent state, and according to recipient category (pancreas alone vs kidney and pancreas). For this study, quality of life was defined as patients' perceptions of their well-being and ability to function in six areas: physical and mental health, social functioning, role (work and home) functioning, overall health perceptions, and physical pain. Patient self-report questions from the Medical Outcome Study were used to provide a score scaled from 0 to 100, for each area. Health status was assessed by sick days, hospitalizations, and emergency room visits. Patients with a successful pancreas graft (N = 65) reported significantly more positive health perceptions (51.9 vs 28.9), less pain (33.9 vs 45.3), and greater ability to function socially (84.9 vs 71.3) than did patients whose pancreas grafts were not successful. In addition, patients with successful pancreas grafts rated their ability to perform routine activities as nearer to normal on the Karnofsky Index (2.82 vs 3.63) and were more likely to view themselves as healthier since the pancreas transplant than were patients whose pancreas grafts were not successful. These effects persisted after statistical adjustment for recipient category and case-mix factors of age, sex, education, and length of time since pancreas transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Quality of life of pancreas transplant recipients.

The quality of life outcome of 131 pancreas transplant recipients who were 1 to 11 years post-transplant were studied. Patients with a functioning pancreas graft (n = 65) described their current quality of life and rated their health significantly more favourably than those with non-functioning grafts (n = 66). For example, of those patients with a functioning pancreas graft, 68% expressed overall satisfaction with their life, 89% felt healthier since their transplant, and 78% reported that they could care for themselves and their routine daily activities. In contrast, of those patients without a functioning graft, only 48% expressed overall satisfaction with life (p less than 0.01), only 25% felt healthier since their transplant (p less than 0.001), and only 56% indicated they could care for themselves and their daily activities (p less than 0.001). Regardless of graft function, the majority of patients were comfortable with their decision to have the transplant, and most of the patients with pancreas graft function reported that they would have another transplant if their graft failed. While successful pancreas transplantation may not elevate all diabetic patients to the level of health and function of the general population, these patients report a significantly better quality of life than do those patients who remain diabetic.

Adult↗

Safety of bronchoalveolar lavage in the critically ill, mechanically ventilated patient.

OBJECTIVE: To assess complications of bronchoalveolar lavage in the intubated, mechanically ventilated patient. DESIGN: A retrospective, consecutive case series. SETTING: Medical, surgical, and bone marrow transplant critical care units at a university teaching hospital. PATIENTS: Ninety-nine consecutive critically ill, mechanically ventilated patients undergoing bronchoalveolar lavage were included in the study. INTERVENTIONS: All patients underwent bronchoalveolar lavage using a standard method designed to maximize the safety of the procedure. MEASUREMENTS: Each patient's hospital chart was reviewed for immediate and delayed medical complications of the procedure, including cardiac arrhythmias, bleeding, and hemodynamic disturbances. Specific indices of lung mechanics (peak inspiratory airway pressure and static compliance) and oxygenation (alveolar to arterial oxygen tension gradient [P(A-a)O2] and the ratio of FIO2/PaO2) were measured before and 4 hrs after bronchoalveolar lavage to assess durable physiologic consequences of the procedure. RESULTS: No complications occurred that required premature termination of bronchoalveolar lavage. Three patients exhibited adverse effects (hypotension in two and wheezing in one) immediately after the procedure, all of which resolved promptly with treatment. No statistically significant changes were observed in the variables of arterial oxygenation or pulmonary mechanics. Although the sample mean did not change significantly for any of the oxygen variables, 19% of the patients experienced widening of the P(A-a)O2 by greater than 100 torr (greater than 13.3 kPa). A systematic analysis indicated that there was no statistically significant relationship between readily available clinical variables (including duration of mechanical ventilation before bronchoalveolar lavage and prebronchoalveolar lavage P[A-a]O2), and deterioration in oxygenation after the procedure. CONCLUSIONS: We conclude that bronchoalveolar lavage is a well-tolerated procedure in critically ill, mechanically ventilated patients, provided that risk factors for complications are corrected before the procedure and one adheres to procedural guidelines focused on patient safety. Clinically important complications are uncommon. Some patients exhibit deterioration in oxygen after bronchoalveolar lavage; this occurrence cannot be predicted before the procedure.

Adolescent↗

Pharmacologic basis for high-dose oral acyclovir prophylaxis of cytomegalovirus disease in renal allograft recipients.

The incidence of cytomegalovirus disease, the most important infectious complication of renal transplantation, was reduced in renal allograft recipients by a regimen of prophylactic high-dose oral acyclovir. To analyze the pharmacologic aspects of our prophylactic approach, we evaluated safety, pharmacodynamics, and in vitro susceptibility data. One hundred four recipients of cadaveric renal allografts received either oral acyclovir (n = 53) in doses of up to 3,200 mg/day or a placebo (n = 51) for 12 weeks posttransplant. Leukocyte count and serum creatinine were selected as markers of laboratory safety and were evaluated pretransplant, at study midpoint (creatinine only), and at study completion. Concentrations of acyclovir in plasma were determined to verify the ability of the dosing strategy to achieve predicted values. Viral resistance was assessed by calculation of in vitro 50% inhibitory concentrations (IC50s) of acyclovir for the cytomegalovirus strains collected from the subjects. Our results showed no difference in leukocyte count or serum creatinine between the acyclovir and placebo recipients. Plasma acyclovir concentrations were maintained within the expected limits and did not differ between patients who developed cytomegalovirus disease and those who did not. The mean acyclovir IC50s for cytomegalovirus isolates were 42.6 mumol/liter in the acyclovir recipients and 48 mumol/liter in the placebo recipients. We conclude that the clinical benefit of high-dose oral acyclovir therapy occurred despite plasma drug concentrations below the mean IC50 for the patient viral isolates. Furthermore, the use of the regimen did not produce leukopenia, adversely affect renal function, or alter the susceptibility of cytomegalovirus strains to acyclovir. This approach and dose adjustment scheme may be appropriate for other immunocompromised patients at risk for cytomegalovirus infection and disease.

Acyclovir↗

The effect of multiple doses of phenylpropanolamine on the blood pressure of patients whose hypertension was controlled with beta blockers.

Single-dose phenylpropanolamine (PPA) can cause blood pressure elevation in healthy volunteers and in patients whose hypertension is controlled with beta blockers. Few data exist on the effect of long-term PPA dosing on blood pressure in normotensive or hypertensive patients. Therefore, we studied the effect of multiple PPA doses in seven hypertensive men whose blood pressure was controlled with beta blockers. These patients had previously demonstrated a mean increase in blood pressure after 25 mg PPA compared to placebo. Each patient received 25 mg PPA 3 times a day for 6.3 days. Five patients completed the study. After drug therapy on days 1 and 7, statistically significant increases in the peak measured systolic and diastolic blood pressures from baseline were found, with ranges of maximum increase 3-22 mm Hg and 0-16 mm Hg, respectively. The peak measured blood pressures on days 1 and 7 were significantly different from placebo values for both systolic and diastolic pressures. The area under the blood pressure-time curve and the change between baseline and peak for systolic and diastolic blood pressures on days 1 and 7 were not significantly different. Tolerance and hypersensitivity were not detected. Several doses of PPA did not alter the blood pressure effect from the first-dose response, however, caution and close monitoring are still necessary for these patients.

Adrenergic beta-Antagonists↗

Knowledge gains from a computer-based health risk appraisal.

During 1990, 83 patients seen for a general physical examination at a family practice clinic completed a computer-based health risk appraisal in one of two formats, batch or interactive. They also completed a written questionnaire on their health risks and knowledge before taking the appraisal, and 65 of them completed another health risk appraisal and questionnaire three months later. No difference in user evaluation of the appraisal regarding its helpfulness, their intent to change behavior based on the appraisal, or amount learned from the appraisal was found between batch and interactive formats. About half (48%) of the individuals correctly estimated their overall health risks before taking the health risk appraisal. Among those who initially misjudged their health risks, few women adjusted their health risk rating at followup. Men showed a tendency to adjust their rating to more closely agree with the health risk appraisal estimates although the differences are not statistically significant. Eighty percent of the men and 55% of the women accurately rated their overall risk at followup. Knowledge of specific causes of death did not improve at followup.

Adult↗

Use of a computer-based health risk appraisal by older adults.

BACKGROUND: A health risk appraisal (HRA) is a tool for health promotion. Conversational microcomputer-based HRAs may be more cost effective than other HRA formats. The acceptability of conversational HRAs, however, has not been demonstrated for older adults. METHODS: We studied the acceptability of a conversational microcomputer-based HRA in a sample of 247 adults at the Minnesota State Fair and the Senior Options Exposition. All users were offered the appraisal via mouse or keyboard interface. Acceptability was measured in terms of user-reported helpfulness, intent to change, time of use, and willingness to view HRA health recommendations. Data on completion time and willingness to view HRA recommendations were collected for Senior Exposition users only. Regression analyses were used to examine the combined impact of interface (mouse or keyboard), location (State Fair or Senior Exposition), age, and sex on user acceptability. Results. Interface and location had no effect on helpfulness or change ratings. Older users rated the appraisal more helpful (P less than .007). Both older and female users reported more intent to change behavior (P = .016, both). Time to use the appraisal was related to interface, age, and sex. Mouse users (P less than .0001), older users (P less than .0001) and female users (P less than .05) took significantly longer to use the appraisal. Significantly more mouse users declined to see recommendations (P less than .02). CONCLUSIONS: Older users can derive as much or more value from conversational health risk appraisals as younger users; however, a mouse interface may be less effective for this age group.

Adult↗

Chronic rejection after liver transplantation: a study of clinical, histopathological and immunological features.

In an effort to better understand chronic liver transplant rejection, we studied 110 children and adults who survived for at least 2 mo after the transplant procedure. Chronic rejection was defined using a combination of clinical and histopathological criteria and was diagnosed in 10 of the 110 patients for an incidence of 9.1%. All 10 patients were children with the mean age 3.4 yr vs. 21.7 yr for patients without chronic rejection (p less than .001). Males and females were equally represented, and nine received a liver from a gender-matched donor. Four patients were non-Caucasian, resulting in an incidence of 21.7% in non-Caucasian recipients vs. 6.6% in Caucasian recipients (p less than .05). All chronic rejection patients received a liver from an ABO-compatible donor. T-cell crossmatch was negative in all patients in whom it was assessed, and no significant disparity in either the class I or class II human leukocyte antigen loci was noted. Patients who had chronic rejection experienced acute rejection earlier, 11 days vs. 16 days (p less than .05), than patients who did not. In 8 of 10 patients, chronic rejection appeared to evolve directly from early episodes of acute rejection that were unresponsive to immunosuppressive therapy. Two distinct histological presentations were noted. One was progressive loss of bile ducts without hepatocellular injury (four patients), and the other was characterized by worsening ischemic hepatocellular damage and fibrosis (six patients) in addition to severe ductular injury. The first was associated with a more benign clinical course, the second with rapidly deteriorating hepatic function. Three patients recovered spontaneously 9 to 14 mo after transplant, one died awaiting a donor for retransplant, and five had retransplants. We conclude that chronic rejection after the operation is a relatively uncommon complication of liver transplantation with a variable clinical course and unpredictable outcome.

Adolescent↗

Liver disease in alpha-1-antitrypsin deficiency: prognostic indicators.

We reviewed the clinical presentation, subsequent course, and outcome of 98 patients with alpha 1-antitrypsin deficiency seen at our institution during the past 20 years to obtain answers to the following questions: (1) What prognostic factors aid in determining the course of liver disease in affected patients? (2) When is the appropriate time for referral to a liver transplant center? (3) Does breast-feeding prevent chronic liver disease? (4) What is the incidence of severe liver disease in family members? Our analysis revealed that the initial values of alanine aminotransferase, prothrombin time, and trypsin inhibitory capacity may have prognostic value. During clinical follow-up the recurrence or persistence of hyperbilirubinemia along with deteriorating results of coagulation studies indicated the need for liver transplantation because of imminent poor outcome. Girls had a worse prognosis than boys. Initial breast-feeding versus feeding of commercial formulas did not influence overall overcome. The incidence of significant liver disease among "at risk" siblings was 21% (3/14); if one assumes mendelian inheritance from heterozygous parents, the overall risk for siblings in our families was 5%.

Adolescent↗

The effect of single-dose phenylpropanolamine on blood pressure in patients with hypertension controlled by beta blockers.

We studied the effect of phenylpropanolamine on blood pressures in seven patients whose hypertension was controlled with beta blockers. Rapid-release phenylpropanolamine 25 mg and placebo were given on separate days according to a double-blind, randomized, two-period crossover design. The crossover analyses detected significant drug effects without carryover or period effects for both systolic and diastolic pressures. The peak systolic blood pressures after phenylpropanolamine averaged 8 mm Hg higher than those measured after placebo. Similarly, the peak diastolic pressures after phenylpropanolamine averaged 4.9 mm Hg higher than those with placebo. Baseline weights, blood pressures, and pulses did not significantly differ between patient groups or change significantly across study periods. Usual single and therapeutic doses of phenylpropanolamine caused small but statistically significant increases in blood pressure. If such changes are not considered when antihypertensive therapy is altered or initiated, patients may receive excessive or unnecessary drugs.

Adult↗

A comparison of response rate, data quality, and cost in the collection of data on sexual history and personal behaviors. Mail survey approaches and in-person interview.

The authors examined differences in rate of response, data quality, and cost between mail approaches and in-person interview in the collection of data on sexual history and personal behaviors. A sample of women from a midwestern United States university (n = 342) was identified from health service medical records as having been seen for a sexually transmitted disease (cases) or a contraceptive visit (controls) during the latter half of 1985. The women were randomly assigned to one of three data collection strategies. A total of 268 subjects (78%) participated. Results indicated no differences in validity by method of data collection or by case-control status but there were significant differences in completeness, cost, and response rates. In-person interviews resulted in more complete data than mail approaches, although all instruments had low proportions of missing data (0.001-0.006). Response rate differences were not found when data collection methodologies were compared (75-82%) but were found in case-control analyses. Cases were consistently less likely to participate and significantly less likely to respond by mail (p less than 0.05). The cost of the in-person interview was approximately four times that of the mail survey for the data collection. Implications of the case-control response rate difference suggest that mail methodologies, although low in cost, may introduce sampling bias in studies of sexually transmitted diseases.

Adolescent↗

Growth failure in cholestatic rats: the effect of malnutrition on insulin-like growth factor I.

Low IGF-I levels are found in patients with chronic liver disease, but it is not known whether these reductions in IGF-I are secondary to hepatic dysfunction or to malnutrition. To determine whether malnutrition associated with hepatic dysfunction causes the decrease in these levels, serum and liver IGF-I concentrations and liver IGF-I mRNA content were compared in three groups of Sprague-Dawley rats: 15 rats underwent bile duct obstruction; 10 rats were sham-operated and pair-fed with operated rats to control for nutritional status; and 12 rats were sham-operated controls fed ad libitum. In addition, IGF-I peptide and mRNA were compared with food intake, crude nitrogen balance, total wt gain, tail length increase and leg muscle wt. All the parameters were lower in cholestatic and nutritionally deprived animals than in control animals (p less than 0.001). There was no difference in serum and hepatic IGF-I and liver IGF-I mRNA values between the 10 cholestatic and pair-fed animals, despite lower crude nitrogen balance, tail length gains, and leg muscle wt in the bile duct-obstructed animals. These studies suggest that in chronic bile duct obstruction, the low serum and hepatic IGF-I levels are primarily due to decreased food intake and appear unrelated to cholestatic liver disease itself. However, factors in addition to suboptimal nutrition and decreased IGF-I levels must also contribute to cholestasis-induced growth failure.

Animals↗