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Biomedical subjects

R W Harris

Publications and source records attributed to R W Harris.

At least 19 recordsLinked to original sources

Failure of gamma-interferon to decrease mortality from group B streptococcal sepsis in neonatal rats.

Newborns possess an altered immune response to infection with impaired leukocyte chemotaxis and deficient production of gamma-interferon (IFN-gamma). IFN-gamma enhances neonatal leukocyte activation and movement. We proposed that IFN-gamma in conjunction with penicillin compared to penicillin therapy without IFN-gamma would increase survival from group B streptococcal sepsis in a neonatal rat model. Newborn rats were infected with 10(5) cfu of group B streptococci at 48-72 h of age and randomized to receive either serum albumin (controls), rat recombinant IFN-gamma, albumin and penicillin, or IFN-gamma and penicillin. Survival 120 h postinfection revealed: controls 5% (1/21); IFN-gamma 4% (1/24); penicillin 23% (5/22); and IFN-gamma plus penicillin 10% (2/21). Survival analysis with a lognormal parametric regression model revealed only the penicillin group to have improved survival compared to controls. Contrasting the penicillin group with the IFN-gamma plus penicillin group did not reveal a statistically significant difference by the Wald chi2 statistic (p = 0.25).

Animals

Size and duration of zidovudine benefit in 1003 HIV-infected patients: U.S. Army, Navy, and Air Force natural history data. Military Medical Consortium for Applied Retroviral Research.

OBJECTIVES: The study's objectives were to determine the size and duration of benefits of early versus delayed versus late treatment with zidovudine (ZDV) on disease progression and mortality in HIV-infected patients, and whether patients rapidly progressing before ZDV treatment had a different outcome from those not rapidly progressing before ZDV. DESIGN: The design was an inception cohort of 1003 HIV-infected patients. One hundred and seventy-four of the 1003 patients were treated before CD4 counts fell to <400 x 10(9)/L, ("early treatment"); 183 of 1003 patients were treated after CD4 counts fell to <400 x 10(9)/L but before clinical disease developed ("delayed treatment"); and 646 of the 1003 patients had either been treated after clinical disease developed or had not been treated at all by the end of follow-up ("late treatment"). Outcomes were progression to clinical HIV disease and mortality. RESULTS: The relative risk (RR) of progression for early versus delayed treatment was 0.58 (p < .03), and durability of ZDV benefits on progression was estimated at no more than 2.0 years; however, this estimate had wide confidence intervals. The RR of progression for delayed versus late treatment was 0.54 p < .0001, and durability of ZDV benefits was estimated at 1.74 years; this estimate had narrow confidence intervals. Survival was better for the early versus delayed treatment (RR = 0.55), but this difference was not statistically significant. In the subgroup of patients with more rapid CD4 decline prior to ZDV therapy, significant benefits on progression were observed for early versus delayed ZDV therapy (RR = 0.42, p = .02) and delayed versus late ZDV therapy (RR = 0.51; p = .0004). Duration of benefit was estimated to be 4.5 years (early versus delayed) and 1.7 years (delayed versus late). For patients with less rapid pre-ZDV decline in CD4 levels, a significant progression benefit was observed for delayed versus late therapy (RR = 0.50; p = .02). Duration of benefit in this subgroup was estimated to be 1.8 years. No significant benefit was found for early versus delayed treatment (RR = 1.12) in the less rapid pre-ZDV CD4 cell decline subgroup. CONCLUSIONS: Early treatment compared with delayed treatment was associated with a sizable reduction in HIV progression, but the duration of benefits was estimated to last only about 2 years. Delayed treatment compared with late treatment with ZDV was associated with substantial reduction of progression, but this reduction was also clearly limited in duration. Benefits on progression and mortality for the early treatment group were heavily dependent on the pre-ZDV CD4 slope. In the subgroup of patients with the most rapid pre-ZDV CD4 cell declines, the duration of benefit was much longer, possibly as long as 4 years.

Adult

Attempt to correlate urine arsenic excretion with clinical course during melarsoprol therapy of patients with Rhodesian trypanosomiasis.

This study enrolled 28 CNS-involved patients with Trypanosoma brucei rhodesiense at the Kenya Trypanosomiasis Research Institute (Alupe, Kenya) to examine treatment efficacy and toxicity of melarsoprol in relation to renal excretion/dose relationships. This study complied with World Health Organization treatment recommendations, initially treating with suramin followed by three courses of melarsoprol. Traced study patients had a relapse rate of 4.1%. The toxicity and crude death rate was 7.1%. Total urine arsenic output was measured between 24 and 48 hr after the last dose for each course. The range of means of total urine arsenic output between the three treatment courses was 356-511 micrograms. There was no correlation comparing melarsoprol dose, estimated creatine clearance, or urine arsenic output. Urinary pharmacokinetic parameters are not predictive of toxicity or therapeutic efficacy.

Adolescent

Management of arterial occlusive disease following radiation therapy.

Clinically significant arterial occlusive disease developed in 26 patients at between 5 months and 44 years (mean(s.d.) 10.7(12.0) years) following radiation therapy. Therapeutic radiation was associated with lesions of the carotid artery (nine patients), subclavian-axillary arteries (seven) and the abdominal aorta and its branches (10). Clinical presentations included transient ischemic attack, stroke, vertebrobasilar insufficiency, carotid bruit, upper- or lower-extremity ischemia and renovascular hypertension. Surgery for cerebrovascular insufficiency included carotid endarterectomy with vein patch, interposition grafting or subclavian-to-carotid bypass. Carotid or subclavian-to-axillary bypass was performed for upper-extremity ischemia. A combination of endarterectomy and Dacron or saphenous vein grafts was used for infrarenal reconstruction. Tunnels were placed orthotopically. Musculocutaneous flaps assisted in healing selected wounds. Ureteral catheters were useful adjuncts in abdominal vascular reconstructions. There were no operative deaths, strokes or amputations. One patient had recurrent transient ischemic attacks following subclavian-to-carotid bypass. The mean(s.d.) postoperative follow-up was 48.1(39.6) months. Patients presenting with end-organ ischemia following radiation therapy can be managed successfully with aggressive surgical revascularization using a broad spectrum of reconstructive techniques.

Aged

Subclavian artery catheterization: a new approach for endovascular procedures.

PURPOSE: Percutaneous access to the arterial system for endovascular procedures is usually achieved through the femoral arteries. When femoral access is precluded, the axillary or brachial arteries serve as alternatives. Complications associated with the use of the latter arteries have led us to develop subclavian arterial catheterization. METHODS AND RESULTS: From 1978 to 1993, 569 patients underwent angiography via the subclavian artery (> 99% left subclavian artery); 134 were studies of the aortic arch and brachiocephalic vessels; 435 studies involved the descending and abdominal aorta and its branches and runoff. Coronary arteriography was also feasible. Since 1986, 44 patients have undergone endovascular procedures: 33 percutaneous transluminal angioplasties of the visceral, iliac, femoral, and popliteal arteries and 11 thrombolytic procedures of aortofemoral graft limbs (n = 3) and femoral distal bypasses (n = 8) were performed. Complications (1.2%) included partial pneumothorax (n = 2), hemorrhage requiring operative control (n = 2), causalgia (n = 1) and embolization (n = 2). CONCLUSIONS: Whenever percutaneous femoral catheterization cannot be achieved or an alternate access point is indicated, we select the subclavian approach as an alternative to axillary, brachial or translumbar access. It is safe, expeditious, and versatile for virtually all types of systemic and cardiac catheterization; it is also applicable to thrombolysis and balloon angioplasty.

Adult

Addition of droperidol to patient-controlled analgesia: effect on nausea and vomiting.

A double-blind trial of the effect of droperidol on the incidence of nausea and vomiting in patients using patient-controlled analgesia was carried out in 60 healthy women undergoing abdominal hysterectomy. After a standard anaesthetic including droperidol 2.5 mg as a prophylactic antiemetic, patients were randomly allocated to receive postoperative patient-controlled analgesia with either morphine alone (2 mg.ml-1) or morphine (2 mg.ml-1) with droperidol (0.2 mg.ml-1) added to the syringe. Verbal scores and visual analogue scores for nausea, vomiting, pain and sedation were made at 4, 12 and 24 h postoperatively, and any requirement for intramuscular prochlorperazine noted. There was no difference between the groups at any time in the amount of morphine consumed or in pain scores. At 12 h, patients receiving droperidol experienced significantly less nausea, and over the first 24 h, 31% required prochlorperazine compared with 59.3% of patients not receiving droperidol. The number of patients with sedation at 24 h was significantly greater in the droperidol group. We conclude that the addition of droperidol to morphine both reduces nausea and the need for further antiemetic treatment.

Adult

Allograft vein bypass: is it an acceptable alternative for infrapopliteal revascularization?

PURPOSE: Autogenous vein bypass grafts to infrapopliteal outflow sites have patency and limb salvage rates significantly superior to those obtained with prosthetic grafts. However, when infrageniculate bypass is required for limb-threatening ischemia in the patient lacking suitable autogenous veins, nonautogenous reconstruction or primary amputation are the only other alternatives. METHODS: During a 2-year period we implanted 25 cryopreserved allograft saphenous vein bypass grafts in 24 patients (median age 76 years) with tissue necrosis (20 patients), rest pain (4 patients), or acute ischemia (1 patient); 16 patients were men and 8 were women. As many as six previous revascularizations were performed in 79%; two grafts extended to the infrageniculate popliteal artery; 23 grafts extended to a paramalleolar vessel. RESULTS: Secondary patency at 1 month was 87%, but only 36% at 1 year. Use of warfarin (Coumadin) failed to improve the patency rate (five of nine occlusions treated with Coumadin versus eight of 16 not treated with Coumadin). Only eight of 24 patients are alive with open grafts; nine patients have died. CONCLUSIONS: Unheralded occlusions more typical of prosthetic graft failure tempered the initial enthusiasm and effectiveness of vein allografts. All autogenous options must be exhausted to complete distal, secondary revascularization before resorting to nonautogenous conduits. Use of allograft veins must be viewed with continued skepticism.

Aged

The response times during anaesthesia of pulse oximeters measuring oxygen saturations during hypoxaemic events.

Episodes of desaturation were recorded simultaneously by computer from two Ohmeda Biox 3700 pulse oximeters, one with an ear and one with a finger probe, on patients undergoing anaesthesia. Over a period of 6 months, 28 episodes of desaturation were detected. Analysis of the recordings showed the mean minimum saturations recorded for ear and finger probes were 86.3% and 83.5% respectively (p less than 0.01). The mean delay for finger compared to ear pulse oximetry was 4.4 s (p less than 0.01). Analysis at different saturation levels showed finger probe responses to be significantly slower than ear probe responses at saturations equal to and above 91% (p less than 0.05). At saturation levels of 90% or less no significant difference in probe response times were found.

Adult

Influence of masker bandwidth on binaural masking level differences.

Masking level differences (MLDs) were investigated using masking noise with 160 Hz (amplitude-modulated noise) and 600 Hz (filtered-random noise) bandwidth. One hundred normally hearing subjects received the MLD test under both types of noise. Significant differences between noise types were observed in both N0S pi and N pi S0 conditions; MLDs were larger in amplitude-modulated noise. Consideration of these differences would indicate that older MLD norms based solely on filtered-random noise are invalid for amplitude-modulated noise especially where bandwidth differences in the noise exist. Were the norms for 600-Hz-wide filtered-random noise to be applied to results of MLD testing performed using 160-Hz-wide amplitude-modulated noise, patients with lesions in the central auditory pathway might exhibit normal or borderline normal results. Clinical MLD norms established on one type of noise should not be used to interpret MLD results obtained using a different type of noise.

Adolescent

Isolation of a tryptic fragment from Clostridium perfringens theta-toxin that contains sites for membrane binding and self-aggregation.

Trypsin cleaves Clostridium perfringens theta-toxin (perfringolysin O or PFO) at a single site between residues 303 and 304 (Ohno-Iwashita, Y., Iwamoto, M., Mitsui, K., Kawasaki, H., and Ando, S. (1986) Biochemistry 25, 6048-6053; Tweten, R. K. (1988b) Infect. Immun. 56, 3228-3234) and yields an amino-terminal fragment of 30,208 Da (T1) and a carboxyl-terminal fragment of 22,268 Da (T2). Both peptides were purified by reverse phase chromatography of trypsin-nicked PFO. Neither peptide retained hemolytic activity. Peptide T1 had no apparent effect on the hemolytic activity of PFO, whereas T2 was found to inhibit the hemolytic activity of PFO and was analyzed further. The order of binding of T2 and PFO to membranes did not alter the inhibitory effect of T2 on PFO-induced hemolysis, indicating that competitive binding by T2 for PFO membrane binding sites was not the basis for the observed inhibition. Further analysis showed that T2 could inhibit membrane-dependent fluorescence energy transfer (FET) between PFO molecules labeled with fluorescein (fluorescent donor) or tetramethylrhodamine (fluorescent acceptor). This provided evidence that T2 could complex with PFO. T2 was also found to be incapable of self-aggregation (as opposed to PFO), since preincubation of T2 with either erythrocytes or erythrocyte ghost membranes did not affect the T2-dependent inhibition of hemolysis or FET. These data indicate that T2 inhibits PFO-dependent hemolysis by forming a complex with PFO, which inhibits aggregation and that the membrane binding site and a single aggregation site remain intact on T2.

Bacterial Toxins

Kinetic aspects of the aggregation of Clostridium perfringens theta-toxin on erythrocyte membranes. A fluorescence energy transfer study.

Fluorescence resonance energy transfer was used to monitor aggregation kinetics of the "thiol-activated" cytolysin (perfringolysin O (PFO) or theta-toxin) of Clostridium perfringens on erythrocyte membranes. PFO was labeled with the isothiocyanate derivatives of either fluorescein or tetramethylrhodamine. No detectable change in the hemolytic activity of PFO was detected after modification with either fluorophore at a ratio of 1:2 fluorophore molecules/cytolysin molecule. Fluorescence energy transfer (FET) between the donor (fluorescein.PFO or PFOD) and the acceptor (tetramethylrhodamine.PFO or PFOA) was detected by both quenching of donor fluorescence (520 nm) and by enhancement of acceptor fluorescence (575 nm) upon aggregation of labeled cytolysin molecules. FET was only observed when PFOD and PFOA were incubated in the presence of membranes. FET was not observed when PFOD and PFOA were incubated in a membrane-free solution or when unlabeled toxin was substituted for PFOA. FET was also found to be temperature-dependent. The temperature-dependent rates of change in FET upon mixing labeled toxin with erythrocyte membranes proceeded without a lag phase and displayed an activation energy of 18.7 kcal/mol. At all temperatures aggregation of PFO was virtually complete before the onset of hemolysis, the latter exhibiting a distinct lag phase. The lag period before onset of hemolysis was temperature-dependent and exhibited an activation energy of 23.2 kcal/mol. These results suggest that the aggregation of membrane-associated PFO is necessary to initiate the hemolytic process, and the lag phase which occurs before onset of hemolysis reflects the kinetics of PFO monomer to polymer conversion.

Bacterial Toxins

Percutaneous transluminal angioplasty of the lower extremities by the vascular surgeon.

As vascular surgeons, we performed 376 percutaneous transluminal angioplasties as follows: aorta and iliac arteries (148), infrainguinal arteries (191), and bypass grafts (21). Sixteen procedures were attempted but not completed. Neodymium-yttrium-aluminum-garnet laser thermoprobe was successfully used prior to balloon dilatations in 49 procedures. In contrast to our experience with operative intervention, percutaneous transluminal angioplasty was performed more frequently for claudication (75%), nondiabetics (72%), and women (45%). Median age was 71 years. Percutaneous transluminal angioplasty either preceded or followed proximal or distal open reconstruction in 58 extremities. Primary patency rates for iliac percutaneous transluminal angioplasties were: 94% at one month, 93% at six months, and 88% at one year. For infrainguinal percutaneous transluminal angioplasties they were 95%, 82%, and 70% at 1, 6, and 12 months, respectively. Repeat percutaneous transluminal angioplasty increased the one-year patency rates to 92% and 86% for iliac and infrainguinal percutaneous transluminal angioplasties, respectively. Preliminary data indicate that the six-month secondary patency rates were 82% for laser-assisted percutaneous transluminal angioplasty and 65% for percutaneous transluminal angioplasty of distal bypass grafts. The implementation of balloon angioplasty was facilitated by our 21 years of experience with arteriography. Percutaneous transluminal angioplasty has become a valuable adjunct to the practice of vascular surgery by expanding the therapeutic options for managing peripheral vascular occlusive disease.

Aged

The effects of digital quantization error on speech intelligibility and perceived speech quality.

The effects of digital quantization error upon speech intelligibility and perceived speech quality, for normally hearing subjects, were investigated for digitized speech processed to simulate 6-, 8-, 10-, 12-, 14-, and 16-bit integer conversion and 2-, 3-, 4-, 5-, 6-, and 7-bit floating-point conversion. For the integer data, there were no significant differences in speech intelligibility for 8- to 16-bit conversion. Only 6-bit integer conversion at 55 dB SPL resulted in a significant degradation in speech intelligibility. For the floating-point data, there were no significant differences in speech intelligibility for 2- to 7-bit floating-point conversion. However, results of the perceived quality experiment appeared to be more sensitive to differences among the various conditions. Speech processed using 12-, 14-, and 16-bit integer conversion was judged to be superior to speech processed using the 6-, 8-, and 10-bit integer conditions. Speech processed using 5-, 6-, and 7-bit floating-point conversion was judged to be superior to speech processed using 2-, 3-, and 4-bit floating-point conversion.

Acoustics

A case-control study of dietary carotene in men with lung cancer and in men with other epithelial cancers.

Dietary carotene intake during the year before diagnosis was estimated for 96 men with lung cancer, 75 men with other epithelial cancers, and 97 hospital controls. Relative to those of men in the lowest third of carotene intake (less than 1,683 micrograms/day), the smoking-adjusted odds ratios for men in the middle (1,683-2,698 micrograms/day) and upper (greater than 2,698 micrograms/day) thirds of carotene intake were 0.67 and 0.45, respectively, for lung cancer (one-sided test for trend, p = 0.048) and 0.63 and 0.65, respectively, for other epithelial cancers (one-sided test for trend p = 0.074). The protective effect of estimated dietary carotene intake was considerably stronger than was the effect of total intake of carotene-rich vegetables and fruits (grams per day), providing some evidence that the protective factor is carotene itself rather than another component of vegetables and fruits.

Aged