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Biomedical subjects

J Creighton

Publications and source records attributed to J Creighton.

7 recordsLinked to original sources

Antiretroviral use and other risks for HIV-associated neuropathies in an international cohort.

OBJECTIVE: To explore the association between specific nucleoside reverse transcriptase inhibitors and sensory neuropathies (SNs) and define the modifying roles of hepatitis C (HCV), vitamin B12 deficiency, and impaired glucose tolerance. METHODS: The authors conducted a prospective cohort study of 147 HIV-infected adults at two sites chosen to emphasize demographic differences. Standardized assessments included detailed antiretroviral histories, neurologic examinations, skin biopsies for epidermal nerve quantitation, and quantitative sensory testing. RESULTS: There were significant differences between subjects at Johns Hopkins University (JHU) and Monash University (MU) in gender, race, HIV transmission route, and HCV seroprevalence. Symptomatic SN was present in 49% at JHU and 55% at MU (chi2 = 4.02, p = 0.134) and was significantly more common in those at least age 40 than younger patients (odds ratio [OR] = 2.87, 95% CI = 1.27, 6.49). After adjusting for site, age, and CD4 cell count, exposure to didanosine (ddI) or stavudine (d4T) was associated with an significantly increased likelihood of symptomatic SN (ddI: OR = 3.21, 95% CI: 1.56, 6.60; d4T: OR = 7.66, 95% CI: 2.89, 20.33). Plasma HIV RNA, lactate, and HCV were not associated with SN. Quantitative vibratory testing identified neuropathy with a positive predictive value of 76% and epidermal nerve fiber densities 59%. CONCLUSIONS: Exposure to stavudine and didanosine was significantly associated with a heightened risk for symptomatic sensory neuropathy. Reduced vibration thresholds and epidermal nerve fiber densities had the highest diagnostic efficiency of the laboratory indicators of neuropathy examined, but were relatively insensitive in isolation.

Adult↗

Control of cAMP in lung endothelial cell phenotypes. Implications for control of barrier function.

Pulmonary microvascular endothelial cells (PMVECs) form a more restrictive barrier to macromolecular flux than pulmonary arterial endothelial cells (PAECs); however, the mechanisms responsible for this intrinsic feature of PMVECs are unknown. Because cAMP improves endothelial barrier function, we hypothesized that differences in enzyme regulation of cAMP synthesis and/or degradation uniquely establish an elevated content in PMVECs. PMVECs possessed 20% higher basal cAMP concentrations than did PAECs; however, increased content was accompanied by 93% lower ATP-to-cAMP conversion rates. In PMVECs, responsiveness to beta-adrenergic agonist (isoproterenol) or direct adenylyl cyclase (forskolin) activation was attenuated and responsiveness to phosphodiesterase inhibition (rolipram) was increased compared with those in PAECs. Although both types of endothelial cells express calcium-inhibited adenylyl cyclase, constitutive PMVEC cAMP accumulation was not inhibited by physiological rises in cytosolic calcium, whereas PAEC cAMP accumulation was inhibited 30% by calcium. Increasing either PMVEC calcium entry by maximal activation of store-operated calcium entry or ATP-to-cAMP conversion with rolipram unmasked calcium inhibition of adenylyl cyclase. These data indicate that suppressed calcium entry and low ATP-to-cAMP conversion intrinsically influence calcium sensitivity. Adenylyl cyclase-to-cAMP phosphodiesterase ratios regulate cAMP at elevated levels compared with PAECs, which likely contribute to enhanced microvascular barrier function.

Adenylyl Cyclases↗

Comparison of fixed-wire and over-the-wire balloon dilatation systems for percutaneous transluminal coronary angioplasty.

There is controversy concerning the relative safety and efficacy of the 2 currently available percutaneous transluminal coronary angioplasty dilatation systems--fixed-wire (FW) and over-the-wire (OW). A randomized, prospective trial comparing the 2 systems was performed to examine this controversy. Of 1,513 patients undergoing percutaneous transluminal coronary angioplasty at 3 centers between June 1990 and October 1991, 602 (40%) fulfilled the eligibility criteria for the study. There were 643 lesions, of which 327 were randomized to FW and 316 to OW systems. There was no difference in the success rate between FW (92%) and OW (94%) systems. Inability to cross with a wire was infrequent with either system (FW: 1.8%; and OW: 1.6%). Inability to cross with a balloon when the wire crossed the lesion did not occur. An FW system was successful in 6 cases (1.9%) in which the OW system had been unsuccessful, whereas an OW system succeeded in 14 (4.3%) after the FW system had been unsuccessful (p = NS). Time to cross stenoses was 200 +/- 21 and 233 +/- 22 seconds, procedural time was 21 +/- 1.3 and 21 +/- 1.0 minutes, fluoroscopy time was 6.7 +/- 0.4 and 7.1 +/- 0.4 minutes, contrast used was 89.0 +/- 4.2 and 84.0 +/- 3.5 ml, and number of cine runs was 5.9 +/- 3.0 and 6.3 +/- 3.4 in the FW and OW systems, respectively. Complications were infrequent with either system (FW: 10.4%; and OW: 9.5%). Acute closure occurred in 1.8 and 2.2% of cases in the FW and OW systems, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Ontogeny of light-induced decrease of N-acetyltransferase activity in explanted chick pineal glands.

The ontogeny of chick pineal serotonin N-acetyltransferase (NAT) activity was investigated in explanted chick pineal glands at 4, 10 and 21 d of age. Nocturnal levels of the enzyme and the response of the enzyme to light exposure were determined in pineal glands maintained in short-term culture at each age. The results indicate that nocturnal NAT activity was increased in the glands from older birds. Nocturnal levels of NAT activity at the time of the initiation of the experiment were threefold greater in glands from 21-d-old birds as compared to that in glands from 4-day-old chicks. The response to light was similar in all three ages examined; light induced a significant decrease in NAT activity within 60 min in explanted glands from 4-d-old chicks and within 180 min in the glands from the 10- and 21-d-old chicks. A paradoxical transient increase in enzyme activity occurred immediately (within 5 min) following light exposure which was significant in the glands from the youngest chicks, and present, but more variable, in the older chicks. These data indicate that the nocturnal enzyme activity is greater in glands from older birds, but that light exposure of explanted glands initiates a transient rise followed by a decrease in NAT activity at all three ages.

Acetyltransferases↗

Surgical correction of spastic equinovarus deformity in the adult head trauma patient.

The results of 59 surgical procedures for correction of spastic equinovarus deformity of the foot using the split anterior tibial tendon (SPLATT) were reviewed in 54 adults with traumatic head injury. The mean time of follow-up was 49.7 months. Thirty-nine individuals had hemiplegic involvement, three had triplegic involvement, and 12 were quadriplegic. Evaluation of the patterns of lower extremity muscle activity preoperatively by dynamic electromyography in 33 patients showed no significant difference from that seen in the hemiplegic stroke population, namely, spastic calf muscles with overactive toe flexors and anterior tibial muscle. At follow-up all feet were in a plantigrade position. The only complication was a superficial skin slough on the dorsum of the foot which healed uneventfully. Postoperatively, 18 extremities (31%) were brace-free. Forty-one extremities required support because of calf weakness, ataxia, or proprioceptive deficits. Of the 15 patients who were nonambulatory prior to surgery, nine (60%) became ambulatory. At follow-up 36 patients (67%) were independent ambulators, four (7%) required supervision assistance, two (4%) required standby assistance, and six (11%) required minimal assistance. The six individuals (11%) who remained maximally assisted or nonambulatory had improved wheelchair positioning and shoe wear. These results show that the split anterior tibial tendon transfer is a safe and effective procedure for the head trauma patient since it corrects the equinovarus deformity, allowing for improved shoe wear and wheelchair positioning in the nonambulatory individual and improved ambulation with decreased brace wear in the more functional patient.

Adolescent↗