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T R Johnson

Publications and source records attributed to T R Johnson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.

Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.

Adrenergic alpha-Agonists↗
PubMed2000

DX-8951f, a hexacyclic camptothecin analog, on a daily-times-five schedule: a phase I and pharmacokinetic study in patients with advanced solid malignancies.

PURPOSE: To assess the feasibility of administering DX-8951f (exatecan mesylate), a water-soluble, camptothecin analog, as a 30-minute intravenous infusion daily for 5 days every 3 weeks, determine the maximum-tolerated dose (MTD) and pharmacokinetic (PK) behavior of DX-8951f, and seek preliminary evidence of anticancer activity. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of DX-8951f. After three patients were treated at the first dose level, doses were to be escalated in increments of 100%, using a single patient at each dose level unless moderate toxicity was observed. The MTD, defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%, was calculated separately for minimally pretreated (MP) and heavily pretreated (HP) patients. The PK and excretory profiles of DX-8951, the anhydrous form of DX-8951f, were also characterized. RESULTS: Thirty-six patients were treated with 130 courses of DX-8951f at six dose levels ranging from 0.1 to 0.6 mg/m(2)/d. Brief, noncumulative neutropenia was the most common toxicity observed. Severe myelosuppression (neutropenia that was protracted and/or associated with fever and/or severe thrombocytopenia) was consistently experienced by HP and MP patients at doses exceeding 0.3 and 0.5 mg/m(2)/d, respectively. Nonhematologic toxicities (nausea, vomiting, and diarrhea) were also observed, but these effects were rarely severe. Objective antitumor activity included partial responses in one patient each with platinum-resistant extrapulmonary small-cell and fluoropyrimidine- and irinotecan-resistant colorectal carcinoma, and minor responses in patients with prostate, hepatocellular, thymic, primary peritoneal, and irinotecan-resistant colorectal carcinomas. The PKs of total DX-8951 were linear and well fit by a three-compartment model. CONCLUSION: The recommended doses for phase II studies of DX-8951f as a 30-minute infusion daily for 5 days every 3 weeks are 0.5 and 0.3 mg/m(2)/d for MP and HP patients, respectively. The characteristics of the myelosuppressive effects of DX-8951f, paucity of severe nonhematologic toxicities, and antitumor activity against a wide range of malignancies warrant broad disease-directed evaluations of DX-8951f on this schedule.

Adult↗
PubMed2000

Endocarditis attributable to group A beta-hemolytic streptococcus after uncomplicated varicella in a vaccinated child.

Varicella is generally a benign, self-limited childhood illness; however, severe, life-threatening complications do occur. A live, attenuated vaccine exists to prevent this illness, but controversy remains concerning the need to vaccinate children for what is generally a benign, self-limited disease, although more states are currently recommending this vaccine. We report a previously healthy 3-year-old who developed varicella 6 months after vaccination with no apparent skin superinfections, who subsequently developed group A beta-hemolytic streptococcus (GABHS) bacteremia resulting in endocarditis of a normal heart valve. We are unaware of previous reports of endocarditis related to GABHS after varicella. After developing a harsh, diastolic murmur that led to an echocardiogram, aortic valve endocarditis was diagnosed. A 6-week course of intravenous penicillin G was administered. Two weeks after the initiation of therapy, the diastolic murmur was harsher, and echocardiography revealed a large vegetation on the posterior leaflet of the aortic valve, with severe aortic insufficiency and a dilated left ventricle. The patient subsequently developed congestive heart failure requiring readmission and aggressive management. One month after the initial echocardiogram, a repeat examination revealed worsening aortic regurgitation and mitral regurgitation. The patient received an additional 4 weeks of intravenous penicillin and gentamicin followed by aortic valve replacement using the Ross procedure. Our patient, the first reported case of bacteremia and endocarditis from GABHS after varicella, illustrates the need for the health care practitioner to consider both common and life-threatening complications in patients with varicella. While cellulitis, encephalitis, and septic arthritis may be readily apparent on physical examination and commonly recognized complications of varicella, the possibility of bacteremia without an obvious skin superinfection should also be entertained. The case we report is unique in that the patient had normal immune function, had been previously vaccinated, and developed a rare complication of varicella-endocarditis-in a structurally normal heart with a previously unreported pathogen. Although a child may have been vaccinated against varicella, the chance of contracting the virus still exists and parents should be informed of this risk. group A beta-hemolytic streptococcus, endocarditis, varicella, Varivax, complications of varicella.

Aortic Valve Insufficiency↗
PubMed2000

Impact of dietary protein amount and rumen undegradability on intake, peripartum liver triglyceride, plasma metabolites, and milk production in transition dairy cattle.

Feeding strategies of transition dairy cows contribute to the risk factors associated with metabolic disorders that limit production in the ensuing lactation. To investigate the effects of prepartum dietary crude protein (CP) concentration and amount of rumen-undegradable protein (RUP) on postpartum health and production, 44 multiparous Holstein cows were blocked by expected calving date and assigned to one of four isoenergetic prepartum rations beginning 28 d prior to expected calving date. Prepartum rations were: 12% CP and 26% RUP, 16% CP and 26% RUP, 16% CP and 33% RUP, or 16% CP and 40% RUP on a dry matter basis. All cows were fed the same postpartum diet (18% CP, 40% RUP) from 1 to 56 d in milk (DIM). Prepartum dry matter intake (DMI) was not different among dietary treatments. Mean postpartum intakes (kg/d) were higher through 56 DIM (P<0.05) for cows fed the 12% CP:26% RUP diet prepartum compared with any of the 16% CP diets (21.8 vs. 19.8, 18.6 and 18.6; 12% CP:26% RUP vs. 16% CP:26% RUP, 16% CP:33% RUP and 16% CP:40% RUP). There was a DIM x prepartum diet interaction (P<0.05) with the greatest effect of the 12% CP:26% RUP diet evident during the first 35 DIM. Cows fed the 12% CP:26% diet during the transition period tended to produce more milk (kg/d) (P = 0.08) than did cows fed any of the 16% CP diets (40.8 versus 37.8, 38.7, and 37.4; 12% CP:26% RUP vs. 16% CP:26% RUP, 16% CP:33% RUP, and 16% CP:40% RUP). Additional protein (12 vs. 16% CP) in the prepartum diet tended to decrease milk protein (P = 0.10) and milk fat yield (P = 0.08) but did not alter percent milk fat, percent milk protein, or MUN. Liver triglyceride (TG) expressed as milligrams of TG per microgram of DNA or percentage of dry matter (DM) on d -28, -14, +1, +28, and +56 relative to calving were not significantly different among treatments. Maximal (P<0.05) infiltration of TG in liver was observed on +1 d when expressed as a percentage of DM and on +28 d when expressed as milligrams of TG per microgram of DNA. Plasma glucose, calcium, urea nitrogen, beta-hydroxybutyrate, and nonesterified fatty acids were not different (P<0.05) among treatments. The data indicate carryover effects of prepartum dietary protein on postpartum intake and milk production, pointing to beneficial effects of maintaining dietary protein for dairy cows in late gestation at 12% CP.

Animal Nutritional Physiological Phenomena↗
PubMed1999

Self-reported exercise tolerance and the risk of serious perioperative complications.

BACKGROUND: Impaired exercise tolerance during formal testing is predictive of perioperative complications. However, for most patients, formal exercise testing is not indicated, and exercise tolerance is assessed by history. OBJECTIVE: To determine the relationship between self-reported exercise tolerance and serious perioperative complications. METHODS: Our study group consisted of 600 consecutive outpatients referred to a medical consultation clinic at a tertiary care medical center for preoperative evaluation before undergoing 612 major noncardiac procedures. Patients were asked to estimate the number of blocks they could walk and flights of stairs they could climb without experiencing symptomatic limitation. Patients who could not walk 4 blocks and climb 2 flights of stairs were considered to have poor exercise tolerance. All patients were evaluated for the development of 26 serious complications that occurred during hospitalization. RESULTS: Patients reporting poor exercise tolerance had more perioperative complications (20.4% vs 10.4%; P<.001). Specifically, they had more myocardial ischemia (P = .02) and more cardiovascular (P = .04) and neurologic (P = .03) events. Poor exercise tolerance predicted risk for serious complications independent of all other patient characteristics, including age (adjusted odds ratio, 1.94; 95% confidence interval, 1.19-3.17). The likelihood of a serious complication occurring was inversely related to the number blocks that could be walked (P = .006) or flights of stairs that could be climbed (P = .01). Other patient characteristics predicting serious complications in multivariable regression analysis included history of congestive heart failure, dementia, Parkinson disease, and smoking greater than or equal to 20 pack-years. CONCLUSION: Self-reported exercise tolerance can be used to predict in-hospital perioperative risk, even when using relatively simple and familiar measures.

Aged↗
PubMed1999

Multigeneration reproductive toxicity assessment of 60-Hz magnetic fields using a continuous breeding protocol in rats.

Male and female reproductive functions have been proposed as possibly sensitive targets for the biological effects of 60-Hz (power frequency) magnetic fields (MF). However, experimental data relevant to this hypothesized association are very limited. In the present study, the "reproductive assessment by continuous breeding" design was used to identify possible effects of MF exposure on reproductive performance, fetal development, and early postnatal growth in rats. Groups of age-matched Sprague-Dawley rats (40 breeding pairs/group) were exposed continuously (18.5 hr per day) to linearly polarized, transient-free 60-Hz MF at field strengths of 0 Gauss (G; sham control), 0.02 G, 2.0 G, or 10.0 G. An additional group of 40 breeding pairs received intermittent (1 hr on/1 hr off) exposure to 10.0 G fields. F0 breeding pairs were exposed to MF or sham fields for 1 week prior to mating, during a 14-week period of cohabitation, and during a 3-week holding period after cohabitation. The duration of the cohabitation period was selected to be sufficient for the delivery of five litters in the sham control group. Pups from the final F1 litter from each breeding pair were exposed to MF or sham fields until sexual maturity, were cohabitated in MF or sham fields for 7 days with nonsiblings from the same exposure group, and were held in the MF or sham fields for 22 days to permit delivery of F2 pups for evaluation. No evidence of exposure-related toxicity was identified in any rat in the F0, F1, or F2 generations. Fetal viability and body weights in all litters of groups exposed to MF were comparable to those of sham controls. No significant differences between sham controls and MF-exposed groups were seen in any measure of reproductive performance (litters/breeding pair, percent fertile pairs, latency to parturition, litter size, or sex ratio) in either the F0 or F1 generation. Exposure of Sprague-Dawley rats to 60-Hz MF strengths of up to 10.0 G either during their peak reproductive period (F0) or during gestation and throughout their life span (F1) has no biologically significant effects on reproductive performance. These results do not support the hypothesis that exposure to pure, linearly polarized 60-Hz MF is a significant reproductive or developmental toxicant.

Animals↗
PubMed1999

Design, construction, and validation of a large capacity rodent magnetic field exposure laboratory.

A magnetic field exposure laboratory has been constructed to support National Toxicology Program studies for the evaluation of the toxicity and carcinogenicity of pure, linearly polarized, 60 Hz magnetic fields in rodents. This dual corridor, controlled access facility can support the simultaneous exposure of 1200 rats and 1200 mice. The facility contains fully redundant electrical and environmental control systems and was constructed using non-metallic materials to maintain low levels of background (ambient), stray, and cross-talk magnetic fields. The exposure module design provides for large uniform exposure volumes with good control of stray and cross-talk fields, while allowing the use of roll-around cage racks for simplified animal husbandry. Stray fields and cross-talk have been further reduced by the inclusion of "steering coils" in each exposure module. Ambient 60 Hz fields (less cross-talk) in all exposure rooms are <0.1 microT (1 mG), and static magnetic fields have been mapped extensively. Magnetic field strength, waveform, temperature, relative humidity, light intensity, noise level, vibration, and air flow in all animal holding areas are tightly regulated, and are monitored continuously during all studies. Field uniformity in the animal exposure volumes is better than -/+l0%; a systematic program of cage, rack, and room rotation controls for possible positional effects within the exposure system. Magnetic fields are turned on and off over multiple cycles to prevent the induction of transients associated with abrupt field level changes. Total harmonic distortion is <3% at all field strengths. The facility has been used to study magnetic field bioeffects in rodent model systems in experiments ranging in duration from 8 weeks to 2 years.

Air Movements↗
PubMed1999

Cytotoxic and tubulin-interactive hemiasterlins from Auletta sp. and Siphonochalina spp. sponges.

Chemical and biological investigations of extracts from the sponge genus Auletta and two collections of Siphonochalina sp. have shown these organisms to be producers of the potent hemiasterlin class of antitumor agents. In addition to the previously known hemiasterlin (1) and hemiasterlin A (2), a new analogue, hemiasterlin C (3), was isolated and identified. The structures of 1 and 2 were assigned based on comparison to literature values, and 3 was identified on the basis of 1H NMR, 13C NMR, COSY, HSQC, and HMBC experiments. The cytotoxic and antitubulin activities of 1-3 were evaluated. In a comparative assay for inhibition of tubulin polymerization, the hemiasterlins were more potent than dolastatin 15 and equipotent with cryptophycin 1, but were somewhat less potent than dolastatin 10.

Animals↗
PubMed1999

Syntheses of (Z)-and (E)-4-amino-2-(trifluoromethyl)-2-butenoic acid and their inactivation of gamma-aminobutyric acid aminotransferase.

(Z)- and (E)-4-amino-2-(trifluoromethyl)-2-butenoic acid (4 and 5, respectively) were synthesized and investigated as potential mechanism-based inactivators of gamma-aminobutyric acid aminotransferase (GABA-AT) in a continuing effort to map the active site of this enzyme. The core alpha-trifluoromethyl-alpha,beta-unsaturated ester moiety was prepared via a Reformatsky/reductive elimination coupling of the key intermediates tert-butyl 2,2-dichloro-3,3,3-trifluoropropionate and N,N-bis(tert-butoxy-carbonyl)glycinal. Both 4 and 5 inhibited GABA-AT in a time-dependent manner, but displayed non-pseudo-first-order inactivation kinetics; initially, the inactivation rate increased with time. Further investigation demonstrated that the actual inactivator is generated enzymatically from 4 or 5. This inactivating species is released from the active site prior to inactivation, and as a result, 4 and 5 cannot be defined as mechanism-based inactivators. Furthermore, 4 and 5 are alternate substrates for GABA-AT, transaminated by the enzyme with Km values of 0.74 and 20.5 mM, respectively. Transamination occurs approximately 276 and 305 times per inactivation event for 4 and 5, respectively. The enzyme also catalyzes the elimination of the fluoride ion from 4 and 5. A mechanism to account for these observations is proposed.

4-Aminobutyrate Transaminase↗
PubMed1999

Alertenone, a dimer of suberosenone from Alertigorgia sp.

Bioassay-guided fractionation of organic extracts of the gorgonian Alertigorgia sp. has yielded the previously known suberosenone (1), a cytotoxic tricyclic sesquiterpene of the quadrone class, and alertenone (2), a dimer of suberosenone. The structure of 2 was determined by spectral analysis; the 1D TOCSY experiment was particularly useful in the structure elucidation. Comparison of the in vitro cytotoxicity of alertenone and suberosenone revealed that the dimeric alertenone was devoid of cytotoxicity below 35 microg/mL. In a hollow-fiber assay model of in vivo activity, suberosenone exhibited some growth inhibition of two of six tumor cell lines tested.

Animals↗
PubMed1999

Vaccination with pertussis toxin alters the antibody response to simultaneous respiratory syncytial virus challenge.

Many bacterial toxins, including pertussis toxin (PT), exert potent adjuvant effects on antibody synthesis to coadministered antigens. In these studies, we examined whether locally or peripherally administered PT similarly altered the antibody isotype selection to replicating virus after intranasal (inl) challenge. Mice primed intramuscularly with PT and inl with respiratory syncytial virus (RSV) produced RSV-specific antibodies of the IgG2a isotype at a level similar to that of unprimed controls, with some increase in IgG1 production. Mice primed inl with both PT and RSV showed elevated RSV-specific IgG1, increased serum IgE levels, and increased interleukin (IL)-4 in lung supernatants. Splenocytes from these animals produced increased IL-4 when stimulated in vitro with RSV or PT antigens after infection. These results suggest that PT can influence the local production of IL-4 to alter the humoral and cellular immune responses to viral infection as well as to coadministered antigens.

Administration, Intranasal↗
PubMed1999

Passive IgA monoclonal antibody is no more effective than IgG at protecting mice from mucosal challenge with respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a mucosally restricted pathogen that can cause severe respiratory disease. Although parenteral administration of sufficient RSV-specific IgG can reduce severity of lower respiratory tract infection in high-risk infants, delivery of antibody by direct airway administration is an attractive alternative. Topical and parenteral administration of an IgA monoclonal antibody (MAb) specific for the RSV F glycoprotein was compared with an IgG MAb, specific for the same antigenic site, for ability to protect mice against RSV infection. Administration of RSV-specific IgG was more effective in reducing RSV titers in lung (4.6 log10 pfu/g) than IgA MAb (3.6 log10 pfu/g) when given intranasally immediately prior to infection (P=.005). RSV titers in the nose were reduced only by prophylactic administration of IgG parenterally. Therefore, topical administration of IgA is no more effective than topically administered IgG and is less effective than systemically administered IgG for protecting against RSV infection.

Administration, Intranasal↗
PubMed1999

Secreted respiratory syncytial virus G glycoprotein induces interleukin-5 (IL-5), IL-13, and eosinophilia by an IL-4-independent mechanism.

The attachment glycoprotein G of respiratory syncytial virus (RSV) is produced as both membrane-anchored and secreted forms by infected cells. Immunization with secreted RSV G (Gs) or formalin-inactivated alumprecipitated RSV (FI-RSV) predisposes mice to immune responses involving a Th2 cell phenotype which results in more severe illness and pathology, decreased viral clearance, and increased pulmonary eosinophilia upon subsequent RSV challenge. These responses are associated with increased interleukin-4 (IL-4) production in FI-RSV-primed mice, and the responses are IL-4 dependent. RNase protection assays demonstrated that similar levels of IL-4 mRNA were induced after RSV challenge in mice primed with vaccinia virus expressing Gs (vvGs) or a construct expressing only membrane-anchored G (vvGr). However, upon RSV challenge, vvGs-primed mice produced significantly greater levels of IL-5 and IL-13 mRNA and protein than vvGr-primed mice. Administration of neutralizing anti-IL-4 antibody 11.B11 during vaccinia virus priming did not alter the levels of vvGs-induced IL-5, IL-13, pulmonary eosinophilia, illness, or RSV titers upon RSV challenge, although immunoglobulin G (IgG) isotype profiles revealed that more IgG2a was produced. vvGs-priming of IL-4-deficient mice demonstrated that G-induced airway eosinophilia was not dependent on IL-4. In contrast, airway eosinophilia induced by FI-RSV priming was significantly reduced in IL-4-deficient mice. Thus we conclude that, in contrast to FI-RSV, the secreted form of RSV G can directly induce IL-5 and IL-13, producing pulmonary eosinophilia and enhanced illness in RSV-challenged mice by an IL-4-independent mechanism.

Animals↗
PubMed1999

Glucose regulation of the IGF response system in chondrocytes: induction of an IGF-I-resistant state.

Nonresponsiveness to the growth-stimulatory actions of insulin-like growth factor (IGF)-I in chondrocytes has been reported in a number of disease states associated with impaired glucose metabolism. Primary rabbit chondrocytes were investigated for changes in their IGF response system [type-I IGF receptor and IGF-binding protein (IGFBP) expression] and in their ability to mount a synthetic response to IGF-I [as 35S-labeled proteoglycan ([35S]PG) production] in media containing varying ambient glucose concentrations. Whereas basal [35S]PG synthetic rate was unaffected by glucose concentration, synthetic responsiveness to IGF-I was lost in media containing <5 mmol/l glucose or in media containing a "diabetic" glucose concentration (25 mmol/l). IGFBP expression, as measured by Northern analysis of mRNA levels and Western ligand blotting of secreted protein levels, was not significantly altered in the different glucose media, nor were there any differences in the cell surface localization of IGFBPs as assessed by affinity cross-linking with 125I-labeled IGF-I, suggesting that IGFBPs do not induce the IGF-I resistance. The nonresponsiveness to IGF-I in reduced glucose occurred with 25-50% reductions in steady-state levels of IGF type-I receptor mRNA and protein. A significant correlation between IGF receptor mRNA level and synthetic response to IGF-I was observed between 0 and 10 mmol/l glucose concentrations, suggesting that the loss of responsiveness in reduced glucose is manifested at the level of transcription and/or receptor mRNA stability. In contrast, nonresponsiveness to IGF-I in chondrocytes in diabetic glucose concentrations occurred without changes in receptor mRNA and protein levels, suggesting that IGF-I resistance was due to post-ligand-binding receptor defects. It is proposed that IGF-I resistance in chondrocytes subjected to inappropriate glucose levels may constitute an important pathogenic mechanism in degenerative cartilage disorders.

Animals↗
PubMed1999

Characteristics of nurse-midwife patients and visits, 1991.

OBJECTIVES: This study describes the patient populations served by and visits made to certified nurse-midwives (CNMs) in the United States. METHODS: Prospective data on 16,729 visits were collected from 369 CNMs randomly selected from a 1991 population survey. Population estimates were derived from a multistage survey design with probability sampling. RESULTS: We estimated that approximately 5.4 million visits were made to nearly 3000 CNMs nationwide in 1991. Most visits involved maternity care, although fully 20% were for care outside the maternity cycle. Patients considered vulnerable to poor access or outcomes made 7 of every 10 visits. CONCLUSIONS: Nurse-midwives substantially contribute to the health care of women nationwide, especially for vulnerable populations.

Adolescent↗
PubMed1998

Population differences affect the interpretation of fetal nonstress test results.

OBJECTIVE: The object of the study was to determine whether population differences exist with respect to outcomes of women with reactive and nonreactive nonstress test results. STUDY DESIGN: An epidemiologic evaluation was conducted on 2579 women who underwent nonstress tests in the Fetal Assessment Center of the Johns Hopkins Hospital within a week of delivery. Risk factors such as hypertension, diabetes, and postterm pregnancy were used in a logistic regression model to evaluate the ability of the nonstress test to predict outcomes including proxies of fetal distress and fetal and neonatal death. The sensitivities, specificities, and predictive values of the nonstress test for predicting these outcomes in cohorts of black and white women were also determined. RESULTS: The nonstress test was consistently more sensitive for black women than for white women in predicting several perinatal outcomes, but specificity and negative predictive value were consistently lower for black women. The positive predictive value for fetal and neonatal death was higher for white women than for black women. Although the nonreactive nonstress test result seemed to be predictive of certain perinatal events, the odds ratio for predicting perinatal mortality in any study population was no greater than when the nonstress test result was reassuring. CONCLUSIONS: Epidemiologic characteristics affecting test results, such as disease prevalence and population differences, may lead to clinically significant differences in outcome prediction when these tests' results are used. These differences should be considered in the implementation of antepartum fetal testing programs.

Adult↗