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Biomedical subjects

K Johnson

Publications and source records attributed to K Johnson.

At least 397 records · Page 22Linked to original sources

Safe and effective treatment of osteoporosis with intermittent slow release sodium fluoride: augmentation of vertebral bone mass and inhibition of fractures.

The value of intermittent slow release sodium fluoride treatment in the management of osteoporosis was studied by a comprehensive metabolic and clinical assessment during a long term trial. Its effect was compared with that of a large dose of 1,25-dihydroxyvitamin D [1,25-(OH)2D] given for a short period preceding each fluoride treatment period in another group of randomly selected patients. The 24 patients in group I (3 idiopathic and 21 postmenopausal) received cyclic treatment in repeated 5-month cycles; each cycle was initiated by 1,25-(OH)2D (2 micrograms/day) for 2 weeks, followed for 3 months by sodium fluoride (slow release, 25 mg twice daily) with 25-hydroxyvitamin D (50 micrograms twice weekly) and calcium supplements (to bring total calcium intake to 1500 mg/day), and was concluded by 6 weeks of 25-hydroxyvitamin D and calcium supplementation without sodium fluoride. The 21 patients in group II (3 idiopathic and 18 postmenopausal) received the same treatment, except for the omission of 1,25-(OH)2D. In both groups, the serum fluoride level was maintained within 5-10 mumol/L (95-190 ng/mL) during fluoride treatment, and serum osteocalcin concentrations correlated positively with the duration of treatment. However, vertebral bone mineral content (L2-L4) did not increase significantly in group I, whereas it rose significantly in group II (fractional change, +0.031/2.4 yr in group I vs. + 0.118/2.9 yr in group II; P less than 0.005). Although bone histomorphometric analyses disclosed overall improvement in both groups, only group II had significant increases in the mineral apposition rate [0.5 +/- 0.2 (+/- SE) to 1.4 +/- 0.2 micron/day; P less than 0.05] and the adjusted apposition rate (0.2 +/- 0.1 to 0.7 +/- 0.1 micron/day; P = 0.04). The vertebral fracture rate significantly declined in both groups, but more so in group II. Excluding the first year of treatment, the fracture rate during treatment in group II of 0.03/patient yr was significantly lower than that of 0.28/patient yr in group I (P less than 0.05). The treatment was well tolerated in both groups; only 16% of patients had either gastrointestinal or rheumatic complications. We conclude that intermittent sodium fluoride treatment without 1,25-(OH)2D provides safe and effective treatment of osteoporosis, marked by formation of new adequately mineralized bone, a rise in vertebral bone mass, and reduced frequency of vertebral fractures. The addition of 1,25-(OH)2D treatment before initiation of each fluoride phase yielded a less favorable response.

Adult↗

Higher formant normalization results from auditory integration of F2 and F3.

Two experiments were conducted to test the hypothesis that higher formant normalization results from the auditory integration of F2 and F3 when they are within 3 Bark of each other. In the first experiment, Formants 3-5 were manipulated in both a "hid"-"head" continuum (in which F2 and F3 are within 3 Bark of each other) and a "hood"-"HUD" continuum (in which F2 and F3 are not within 3 Bark of each other). It was found that there was a shift in identification consistent with the higher formant normalization effect only in the "hid"-"head" continuum. In the second experiment, F3 alone was manipulated in a "hood"-"HUD" continuum. The amplitude of F3 in this continuum was increased (as compared with the F3 in the "hood"-"HUD" continuum used in Experiment 1) and a pretest indicated that the shift in F3 could be detected. As in the first experiment, there was no shift in identification associated with shifting F3 frequency in a back-vowel continuum. The results of these experiments are not consistent with an explanation of higher formant normalization in which hearers adjust an internal vowel space in response to higher formant information; rather, the present findings indicate that higher formant normalization results from auditory integration of F2 and F3.

Adult↗

Kaposi's sarcoma and AIDS: a variable spectrum.

A cohort of 61 patients with Kaposi's sarcoma (KS) and AIDS was seen in the Oncology Unit of the Toronto General Hospital between 1982 and 1986. In an attempt to identify prognostic variables, laboratory and clinical parameters were examined using Kaplan-Meier estimates and the Cox Regression Model. All patients were male, median age 36 years (range 23-52). In 49 patients KS was diagnosed before any AIDS-associated opportunistic infection (OI). Three patients had concurrent KS and OI, and nine patients developed KS one or more months after an OI. Only 11 patients had stage I or II disease, 34 stage III, and 15 stage IV. Only 18 patients (30%) were asymptomatic. Twenty-six percent had fever, night sweats, or weight loss, 11% had minor opportunistic infections, and 33% had both symptom complexes. The median overall survival was 10.5 months. The survival of patients who received chemotherapy for their KS was not significantly different from the survival of non-treated patients (p = 0.7). Although significant differences in survival could not be seen between stages, patients with both systemic symptoms and minor opportunistic infections had significantly shorter survival (p = 0.03). Survival from the onset of KS was significantly shorter for patients who had experienced a previous OI, but their overall survival from the date of diagnosis of AIDS was not significantly different from those patients presenting with KS alone. When analyzed separately the laboratory parameters of hemoglobin (p less than 0.0001), absolute lymphocyte count (p = 0.03), platelet count (p = 0.04), and T4 level (p = 0.05) demonstrated a significant relationship with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Empirical therapy for the management of acute proctitis in homosexual men.

An effective empirical treatment regimen would provide a more rapid and less expensive approach to the management of homosexual men with acute proctitis. We conducted a randomized trial in 129 homosexual men who presented with acute proctitis, comparing treatment with an empirical regimen (4.8 million U of aqueous penicillin G procaine intramuscularly and 1.0 g of probenecid orally, followed by 100 mg of oral doxycycline twice daily for seven days) with specific therapy for each infection as it was recognized. Therapy with the empirical regimen resulted in more rapid resolution of the symptoms of proctitis, the objective signs of proctitis, and the infecting microorganisms. However, nearly one fourth of the patients, primarily those with unrecognized herpes simplex virus proctitis, did not respond to empirical therapy. We recommend empirical therapy coupled with appropriate pretreatment diagnostic testing for the initial management of acute proctitis in homosexual men with no clinical evidence of acquired immunodeficiency syndrome or AIDS-related complex.

Adolescent↗

Acetylcholine sweatspot test for autonomic denervation.

A test for autonomic denervation based on the local sweat response to 0.1 ml 1% acetylcholine administered intradermally, which depends on an intact local sympathetic supply, is described. Diabetic autonomic neuropathy affects the longest fibres first and thus the test was applied to the feet. After painting a standard site on the dorsum of the foot with iodine and starch, acetylcholine was injected intradermally in the centre. The normal response, visible to the eye, is a uniform distribution of dark spots of iodine discolouration at the sites of sweat production. In diabetic autonomic neuropathy this pattern is lost to a varying degree. In a photographic image magnified x 10, the spots were counted in sixty 2.5 cm squares in a grid centred on the injection site. 50 normal volunteers aged 18-69 were tested. No effect of age or sex was found. Five or more squares with less than 6 spots was the definition of abnormal. 24 diabetic men who complained of impotence were investigated with the sweatspot test, a pupil test, and cardiovascular autonomic function tests. 13 had abnormal sweatspot tests with scores up to sixty squares with less than 6 spots. In keeping with the increased length of the sympathetic fibres to the feet compared with those to the iris, there was a 30% false-negative rate for the pupil test if the sweatspot test is taken as standard. Agreement between the cardiovascular tests and the sweatspot test was seen in only 17 patients. The sweatspot test appears to be a more sensitive indicator of autonomic neuropathy than the commonly used cardiovascular tests.

Acetylcholine↗

Reevaluation of the maximum tolerated dose of continuous venous infusion of 5-fluorouracil with pharmacokinetics.

5-Fluorouracil (5-FU) was administered as a continuous ambulatory venous infusion to 25 patients in a Phase I trial. The principal dose limiting toxic effect observed was mucositis. Skin rash and diarrhea occurred less frequently. Hematological toxicity was modest, and no hepatic toxicity was seen. One partial remission of 138 days duration was seen in a patient with metastatic breast carcinoma who was previously refractory to a 5-FU combination regimen. Patient tolerance of 5-FU delivered in this manner appeared highly variable. On the basis of this trial, we recommend that future studies evaluating the efficacy of long-term venous infusion of 5-FU should utilize a dosage of 450 mg/m2/day.

Diarrhea↗

Segregation of linked probes to myotonic dystrophy in a family demonstrating that 152 and APOC2 are on the same side of DM on 19q.

The two markers most closely linked to the myotonic dystrophy (DM) locus on chromosome 19 are the gene that codes for apolipoprotein CII (APOC2) and the anonymous probe D19S19 (LDR152). Both of these markers show tight linkage to DM, with maximum lod scores of greater than 20 at recombination fractions of less than 0.05. We have identified, in a family in which DM segregates, an affected individual where a meiotic recombination event has occurred in which both of these linked markers have crossed over with the gene defect. This demonstrates that APOC2 and D19S19 are probably on the same side of DM.

Chromosome Mapping↗

Conservative treatment of uveal melanoma: probability of eye retention after proton treatment.

Enucleation was performed after proton treatment in 57 of 1006 (5.7%) uveal melanoma patients treated with proton beam therapy at the Harvard Cyclotron Laboratory between July 1975 and December 31, 1986. Only 2% of 99 patients with small tumors and 4% of 566 patients with intermediate size tumors underwent enucleation after treatment; 10% of 341 patients with large tumors lost the treated eye. No eyes were removed after 52 months, with 89% of enucleations performed during the first 36 months after treatment. Eye retention rates at 60 months were 89.1 +/- 3.0% for the entire group, and 97 +/- 3.7%, 92.7 +/- 3.1%, and 78.3 +/- 7.0% in patients with small, intermediate, and large tumors, respectively. Significantly greater enucleation rates were observed in patients with large tumors than in those with intermediate tumors (p = less than .0001), in patients with tumor height greater than 8 mm relative to those with tumors less than or equal to 8 mm, p = (less than .0001), with tumor diameter greater than 16 mm compared to less than or equal to 16 mm, (p = less than .0001), and with tumor involvement of the ciliary body compared to involvement of the choroid only (p = less than .0001). Possible strategies to decrease the likelihood of enucleation in patients at apparently increased risk of losing the eye after conservative therapy, that is, those with large tumors involving the ciliary body, might include a lower total dose, a more protracted treatment course, or a lower radiation dose and adjuvant treatment with chemotherapy and/or immunotherapy, with hyperthermia, or with other radiation sensitizers.

Actuarial Analysis↗

Transformation of rat liver epithelial cells with v-H-ras or v-raf causes expression of MDR-1, glutathione-S-transferase-P and increased resistance to cytotoxic chemicals.

We have examined the relationship between transformation and multidrug resistance by employing the v-H-ras or v-raf oncogenes to transform rat liver epithelial (RLE) cells in vitro. The data indicate that transformation of RLE cells with v-H-ras or v-raf results in increased resistance to the cytotoxins adriamycin, vinblastine and 2-acetylaminofluorene. This multidrug resistance is accompanied by increasing expression of P-glycoprotein (MDR-1) and glutathione-S-transferase P (GST-P). Thus, neoplastic transformation of RLE cells with v-raf or v-H-ras, independently of chemical exposure, results in multidrug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Effect of response criterion on measures of speech understanding in the elderly.

Twenty-four elderly subjects were divided into three groups on the basis of response criterion in a signal-detection task. The groups, representing strict, lax, and intermediate listeners, were then compared on the basis of performance on several conventional speech audiometric measures. When the data were corrected for degree of hearing loss, group differences were not significant. Thus, conventional speech audiometric results did not appear to be significantly influenced by response criterion.

Aged↗

Interactions of age, gender, and sensorineural hearing loss on ABR latency.

The interactive effects of gender, age, and degree of sensorineural hearing loss on the absolute latency of wave V of the auditory brain stem response were analyzed in 325 subjects with cochlear loss. Norms based on these data were then applied to an analysis of the wave V latencies of 87 subjects with retrocochlear loss. Results in the cochlear group revealed interactions between gender and age and between gender and degree of hearing loss. The interactive effect between gender and degree of loss was observed for wave V, but not for waves III or I. Separate gender norms for absolute wave V latency, based on empirical boundaries encompassing 99% of the cochlear group, resulted in a 90% correct identification rate in the 87 subjects with retrocochlear lesion.

Adolescent↗

Maternal and child health services for medically indigent children and pregnant women.

Millions of low-income children and women of childbearing age are completely uninsured. Medicaid, the nation's largest public health financing program for the poor, is an inadequate resource for uninsured families with children. By 1984, the program served only 46% of the poor and near-poor, down from 65% in 1976. To assess the availability of maternity and pediatric services for low income uninsured women and children, a survey of 51 Title V Maternal and Child Health agency officials was conducted in 1986. While nearly all states (48) offer some prenatal care programs for indigent women, restrictive eligibility requirements and limited distribution meant that these programs reached only a small proportion of those in need. Only one state, Massachusetts, offered a truly statewide program to all uninsured pregnant women with incomes under 185% of the poverty level. Twenty-three states reported the existence of inpatient maternity programs for indigent women. Yet these, too, were extremely limited. Sixteen programs restricted funds either to women who participated in certain designated maternity programs or else only to those who were identified as high risk prior to the labor and delivery period. Fifteen state agencies reported that hospitals were denying admission to women about to deliver. Another 13 reported that hospitals were denying admission to women not yet in "active" labor. Six additional states were aware of patient dumping but did not identify the specific populations that were affected. Forty-six states reported the existence of pediatric outpatient programs. However, the majority (30) offered only "well-child" care. Seven states maintained pediatric programs limited to only certain ages of children; three of these imposed an age requirement as low as 2 years or younger. Only two states reported the availability of any pediatric inpatient programs financed or administered by Title V agencies other than those for children with special health care needs.

Child↗