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Biomedical subjects

T J Kennedy

Publications and source records attributed to T J Kennedy.

At least 19 recordsLinked to original sources

Bioequivalency comparison between two gonadotropin-releasing hormone products.

The bioequivalency of 2 gondatropin-releasing hormone (GnRH) preparations, gonadorelin diacetate tetrahydrate and gonadorelin semicarbonate, was compared on the basis of luteinizing hormone (LH)-releasing ability of the 2 products in diestrous dairy cows. Twenty-four cycling, nonlactating Holstein cows were subjected to a double prostaglandin estrus synchronization treatment to simultaneously control stage of the estrous cycle and time factors as potential variables effecting LH responses to the treatments being studied. Circulating progesterone concentration was determined to verify stage of cycle at strategic times throughout the study. Twelve days after the second prostaglandin treatment, all cows were randomly assigned to 1 of 2 groups (n = 12). Each group of 12 cows received single doses (100 micrograms) of either GnRH preparation at the start of each test period in a 2-period crossover design. Serum samples were obtained prior to and at 12 times (10, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1,440 minutes) after treatment and were assayed to determine circulating LH concentration. Significant difference between the 2 GnRH products was not found with respect to: mean concentration of LH in the blood during the 24 hours after treatment; maximal LH concentration; time from treatment to maximal LH concentration; and area under the LH concentration curve from time 0 through each of 7 times after treatment (0.5, 1, 1.5, 2, 4, 8, and 24 hours). These data confirm the bioequivalency of the 2 GnRH products.

Animals

Factors influencing adrenal metastasis in renal cell carcinoma.

The factors predisposing to adrenal metastasis in renal cell carcinoma were reviewed in 695 cases. The overall incidence of adrenal metastasis was 4.3%. The risk of adrenal metastasis correlated with tumors that were on the left side, large and replacing the entire kidney, upper pole in location and of advanced T stage. Nevertheless, microscopic and/or contralateral adrenal metastasis was noted in patients with smaller, lower pole or mid renal tumors. Of 30 patients with adrenal metastasis 9 (30%) had clinical evidence of widespread disease. Among the patients who underwent complete surgical resection 14% had either positive lymph nodes or other non-adrenal metastases. Of the patients undergoing resection 81% died, with a mean postoperative survival of 27 months. Sustained disease-free survival was noted in 3 patients (0.43% of the entire series) whose complete pathological staging was pT1-3b, N0, M0. The need and benefit of adrenalectomy during surgery for renal cell carcinoma are extremely limited.

Adrenal Gland Neoplasms

Graduate education in the biomedical sciences: critical observations on training for research careers.

Several aspects of the processes for the pre- and postdoctoral training of PhDs and the postdoctoral research training of MDs are critically examined. The size of the predoctoral pipeline, the sources of support for the students in it, trends in the annual production of bioscience PhDs, and prospects for growth in opportunities, as defined in increases in availability of public and private funds for research, are catalogued. Evidence for the existence of a surplus of research scientists--based on the size and growth of the pool of postdoctorals, the success rates now being experienced by young postdoctorals in competing for National Institutes of Health (NIH) grants, and the success of young postdoctorals in securing career employment--is evaluated, and the conclusion that the nation is producing too many research scientists is suggested. The pros and cons of "downregulating" the production of scientists are explored, the difficulties of reaching a national consensus on the degree of reduction and the partition of reduction among fields of science and academic institutions and academic departments are described, and the mechanisms conceivably available for accomplishing the task--reducing NIH training funds, autoregulation by academic institutions and/or scientific disciplines, and reliance on the decisions of well-informed (probably by the National Academy of Sciences) degree candidates--are enumerated; a preference for the last of these mechanisms is indicated. The NIH's formal training programs are compared with its informal support of training under research grants; questions that the latter practice raises are identified. The striking disparity between the duration of training for conventional predoctoral PhD candidates and that for dual-degree (MD-PhD) aspirants is noted. The measurement problems of assessing the duration of postdoctoral training are highlighted. The fact that dual-degree scientists seem to compete little, if any, more successfully for the great bulk of NIH research grants than do singly-degreed MDs or PhDs is noted, suggesting the advisability of a fresh and objective review of these dual-degree programs, especially the NIH's Medical Scientist Training Program, to reassess their value in the light of their cost. Some characteristics of careers in the biomedical sciences are outlined. Data are presented on the high turnover rates of first-time-ever entrants into the pool of NIH grantees or, stated otherwise, the relatively low rates of survival of principal investigators (PIs) in the NIH research grant system; a method of estimating the steady-state number of NIH ex- PIs "around" at any given moment is proposed.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Science Disciplines

Clinical efficacy and safety of clenbuterol HCl when administered to effect in horses with chronic obstructive pulmonary disease (COPD).

A field study of 239 horses was conducted to determine the efficacy and safety of clenbuterol HCl, a beta 2-adrenergic bronchodilator, when administered incrementally to effect in the treatment of chronic obstructive pulmonary disease (COPD). The severity of COPD (heaves) and response to treatment was determined by clinical evaluation; an overall 'heaveiness rating' (OHR) was assigned at each observation. The horses were treated orally b.i.d. with clenbuterol (as Ventipulmin Syrup), beginning with the lowest dosage of 0.8 micrograms/kg. On day 10 of treatment at the effective dose (0.8, 1.6, 2.4 or 3.2 micrograms/kg), treatment was either withdrawn (Schedule A) or continued for an additional 20 days (Schedule B). Horses on Schedule A demonstrated a significant improvement in the mean OHR on treatment Day 10 compared to the baseline overall heaveiness rating (BOHR) and a significant increase in the mean OHR (relapse) after the drug was withdrawn. Schedule B horses showed significant improvement (compared to BOHR) on treatment Days 10, 20 and 30. Incremental dosing with clenbuterol provided clinical improvement in 75% of the horses with a lower 95% confidence limit of 71%. Twenty-five percent were nonresponders. A greater percentage of the more severely affected horses required the 3.2 micrograms/kg dosage or were nonresponders compared to horses with a lower BOHR. Side effects of sweating, muscle tremor, and nervousness were of low intensity (mild to moderate) and frequency (< 7% of all observations) due to the regimen of incremental dosing to effect.

Animals

Luteinizing hormone-releasing hormone downstaging of clinical stage C prostate cancer.

A total of 7 patients with clinical stage C prostate cancer determined by digital rectal examination, transrectal ultrasonography, radionuclide bone scanning and serum prostatic acid phosphatase determination was treated with luteinizing hormone-releasing hormone analogues for 2 to 5 months in an attempt to downstage the disease. Although substantial decreases in prostate specific antigen level and prostatic volume occurred, only 2 patients experienced pathological downstaging of disease. We conclude that luteinizing hormone-releasing hormone therapy for downstaging of clinical stage C prostatic cancer is of limited value.

Aged

A prospective study of urologist-performed sonographic evaluation of the urinary tract in patients with prostatism.

In this study 171 consecutive patients hospitalized for prostatectomy were prospectively evaluated by urologist-performed transabdominal ultrasound. The urologist-sonographers were blinded to the results of an excretory urogram (IVP) performed and interpreted by radiologists. All significant upper tract pathology (4 renal cell carcinomas and 1 transitional cell carcinoma of the renal pelvis) identified by an IVP also was detected by ultrasonography. Of 5 clinically silent stones seen on an IVP 4 were identified by sonography. There were 13 patients (7.6%) with severe contrast medium allergies or renal failure who were readily evaluated with ultrasonography. Urologist-performed sonography can safely replace an IVP for routine evaluation of the urinary tract before prostatectomy. Moreover, sonography provided significant additional data on prostate size and post-void residual. However, the cost-effectiveness of upper tract imaging in patients before prostatectomy may be questioned.

Calcinosis

The rising cost of NIH-funded biomedical research?

During the last decade, total appropriations for the NIH have grown in current as well as constant dollars. Constant dollar expenditures for indirect costs and research project grants have increased, as also has the number of the latter, while such expenditures for research centers, training, and research contracts have shrunk. The most impressive redistribution in emphasis has been toward traditional research project grants (R01s). The size of the average R01 award, discounted for inflation, has grown at an annual rate of 1.1% during the last decade and 1.3% since fiscal year (FY) 1970; that of the average research program project (P01) has declined over the same periods, after a slight rise in the early 1970s. Factors contributing to the modest rise in the real (constant-dollar) size of the average R01 are explored. The regularity with which current-services-requirements estimates for the NIH exceed inflation reflects real growth in the program, particularly in the category of research project grants; the artifact of basing calculations on the post-rather than pre-"negotiated" levels of awards in the "current" year; and the extent to which the project periods of awards have been extended. The effect of lengthening project periods is slow to become manifest, but inexorably swells the pool of non-competing awards; decisions in this area undertaken in 1985, and continued at least through FY 1988, could very significantly increase current services requirements in FYs 1991 and 1992.

Financing, Government

Scientific fraud.

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Authorship

Urine dipstick vs. microscopic urinalysis in the evaluation of abdominal trauma.

This study was designed to assess the accuracy of the urine dipstick and its ability to predict injury to the urinary tract when compared to routine urinalysis: 1,485 patients had dipstick and microscopic urinalysis performed as part of their evaluation for blunt and penetrating trauma. Dipstick analysis was recorded as either positive or negative. Microhematuria was defined as greater than 0-1 RBC/HPF on microscopic analysis. Blunt trauma accounted for 1,347 (91%) of the patients and penetrating injuries accounted for 138 cases (9%): 1,209 (81.4%) of the specimens were dipstick negative, and 276 (18.6%) were dipstick positive. False negative results, consisting of a negative dipstick reading and greater than 1 RBC/HPF on microscopic analysis occurred in 100 (6.9%) of the cases. False positive dipstick readings occurred in 64 (4.3%) of the patients. There were no cases of a missed injury in the group of 100 false negatives. Cost savings by conversion to the use of dipsticks would have saved our institution about $63,000 per year. It is concluded that the urinary dipstick is a safe, accurate, and reliable screening test for the presence or absence of hematuria in patients sustaining either blunt or penetrating abdominal trauma.

Abdominal Injuries

Flexible cystoscopy.

Flexible fiberoptic technology was first applied to cystoscopy in 1973, with greatly increased usage since 1982. Most procedures formerly performed with rigid cystoscopes can be done using flexible cystoscopes with minimal or no anesthesia. Patient positioning and precystocopy preparation and draping are simplified with the flexible fiberoptic instruments. Complete examination of the urethra and bladder can be performed with a single-lens system and with the patient in a variety of positions. Fiberoptic cystoscopy is limited in patients who are bleeding or have blood clots in their bladders. Withdrawal of irrigant or bladder drainage is cumbersome, and the fiberoptic image is currently not of the same caliber as that of the rigid-lens systems. Fiberoptic cystoscopy has become the procedure of choice for many urologists for ureteral stenting prior to extracorporeal shock-wave lithotripsy. With the advent of lithotripters that require no anesthesia, this application is likely to broaden. Future applications of flexible cystoscopy may include a flexible videocystoscope for use in diagnostic and therapeutic procedures.

Cystoscopes

Long-term follow-up of fertility in cryptorchid patients.

Sixty-four patients who had unilateral or bilateral orchiopexy for cryptorchism between 1950 and 1960 responded to a questionnaire. Marriage rates were the same as in a control group. Unilaterally cryptorchid patients had normal paternity rates and sperm concentrations on semen analysis. Only 2 of 15 bilaterally cryptorchid patients had fathered children, while severe oligospermia was present in all 10 who had semen analysis performed. Thirty per cent of pexed testes had a cosmetically poor result.

Adult

Computer-assisted practitioner-response system for studying the use of cimetidine.

A computer-assisted practitioner-response system was used to review cimetidine use in one hospital. All patients receiving cimetidine from April 1, 1981, through May 15, 1981, were identified daily using a computerized medication-profile system. A practitioner-response form, which asked the physician to indicate the reason for prescribing cimetidine, was placed in the chart of all patients receiving the drug. When these forms were collected, the reviewer scanned the chart for patient demographic information, duration of cimetidine therapy, and other drugs prescribed that potentially could interact with cimetidine. If the physician did not complete the form, the reviewer checked the chart for prescribing information. Cimetidine was prescribed for 10% (247) of all patients admitted during the study period. Seventy percent of the practitioner-response forms were completed; the indication for cimetidine use was obtained for an additional 20% through chart review. Seventy-five percent of the patients were exposed to a potential drug interaction. The most common reason for prescribing cimetidine was to prevent stress ulcers; only 15% of cimetidine orders were for FDA-approved uses. The computer-assisted practitioner-response system was an efficient method for reviewing cimetidine use. The computerized medication profile facilitated identification of patients receiving the drug, and the practitioner-response form provided the indication-for-use data more quickly than conventional chart review.

Cimetidine

Effects of transient ischemia on nutrient flow and arteriovenous shunting in canine hindlimb.

A canine model was developed to simulate use of a pneumatic tourniquet in the clinical setting in order to study the acute and delayed effects of transient ischemia on limb and tissue blood flow, using radioactive microspheres and electromagnetic flow probes. Experimental femoral artery flow rose markedly after tourniquet ischemia, and remained significantly elevated for 24 hours (p less than 0.01). Blood flow to the rectus femoris and anterior tibial muscles rose significantly (p less than 0.05) immediately after tourniquet ischemia, and the latter remained significantly elevated at 24 hours (p less than 0.05). Blood flow to the skin of the experimental limbs was elevated significantly (p less than 0.05), immediately ater tourniquet ischemia, and at no other time. Blood flow to the nerves did not increase to its maximum until 15 minutes after tourniquet deflation, and by 24 hours was normal. Tibial and femoral marrow blood flow remained significantly lower in the experimental limb throughout the 24-hour period. Ater tourniquet ischemia (300 mmhg; 2 hours), greatly increased femoral artery flow was related to reactive hyperemia in skin, muscle, and nerve. Twenty-four hours after tourniquet deflation, there was a significant increase in femoral artery and anterior tibial muscle blood flow, and significant arteriovenous shunting from the experimental limb. These data suggest that the hemodynamic response to a transient ischemic injury is more prolonged and of greater magnitude than previously believed.

Animals

Evaluation of a teat dip of chlorhexidine digluconate (.5%) with glycerin (6%).

Efficacy of a teat dip containing .5% chlorhexidine digluconate and 6% glycerin was tested on 46 clinically normal cows, each with functional quarters. Twice daily immediately after milking, all teats were exposed to a suspension containing 5 X 10(7) colony forming units of Staphylococcus aureus. After each exposure to the infective broth, the left teats were dipped in teat dip while the right teats remained as untreated controls. The study continued until sufficient number of infections occurred to establish efficacy. Mastitis screening followed standard procedures as established by the National Mastitis Council and identified 24 infected teats in the control group and 6 in the treated group for 75% efficacy. The tested teat dip was effective in reducing the incidence of intramammary infections caused by Staphylococcus aureus under experimental exposure. No chapping or irritation occurred with use of the teat dip.

Administration, Topical

Prophylactic medication with pyrantel to prevent liver condemnation in pigs naturally exposed to Ascaris infections.

The use of pyrantel tartrate (106 mg/kg of feed) as a continuous feed medication was evaluated in 848 finishing hogs for efficacy in preventing Ascaris suum infections, and in reducing liver fibrosis and liver condemnation at slaughter, associated with A suum infections. Liver condemnations due to Ascaris damage were reduced 100% in all pigs given pyrantel, when compared with condemnation in non-medicated controls. None of the livers from any of the medicated animals was condemned, whereas livers from 101 (21%) of 479 nonmedicated pigs were condemned due to extensive hepatic scarring. Pyrantel medication administered for 62, 45, or 28 to 31 days resulted in reductions of total number of livers lesions at slaughter by 93.4%, 80.5%, and 68.6%, respectively. In nearly all cases, hepatic lesions remaining at slaughter of pigs given pyrantel in the feed were less distinct than were lesions found on livers from nonmedicated pigs.

Animals

Effects of tourniquet ischemia and postischemic edema on muscle metabolism.

In vivo interstitial muscle pressures measured by wick catheter, tissue gas tensions measured by mass spectrometer, and glucose and high-energy phosphate metabolism measured fluorometrically were studied in the anterior tibial (AT) and vastus lateralis (VL) muscles of primate limbs during and following tourniquet ischemia (2.5 hours; 400 mm Hg) to elucidate postischemic edema and its metabolic consequences. During ischemia, interstitial pressure in the VL rose, while in the AT it decreased, but 24 hours later pressures in both experimental muscles were significantly greater than those in the controls. In both experimental muscles PO2 decreased significantly within 15 minutes of ischemia. PCO2 increased significantly in the AT at 30 minutes and at 75 minutes in the VL muscle. Twenty-four hours later only PO2 in the experimental AT was significantly different than its matched control. During ischemia glucose and phosphocreatine (CrP) decreased significantly, and G-6-P and lactate increased significantly in both muscles, but at 24 hours glucose levels were 25% lower and G-6-P 16.2% higher in the experimental AT and CrP 34% lower in the experimental VL. This study shows that there are significant acute and delayed alterations in primate muscle metabolism following tourniquet ischemia and suggests that these changes may be related to the anatomic location of the muscle studied and the type of trauma it has sustained.

Animals