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Biomedical subjects

F Smith

Publications and source records attributed to F Smith.

At least 19 recordsLinked to original sources

Focal ventricular thinning caused by indomethacin in the late phase of coxsackievirus B4 murine myocarditis.

Indomethacin has been shown to increase virus titers and to worsen cardiac injury in the acute phase of coxsackievirus B4 murine myocarditis. The authors evaluated the effects of indomethacin on the histopathologic changes in a later phase of this disease after virus clearance. Two-day old CD1 mice were infected with coxsackievirus B4. Ten days later, surviving animals were randomized to receive indomethacin or saline intraperitoneally for 10 days. They were then euthanatized, and their hearts were examined for the presence of inflammation, necrosis, scarring, and focal thinning. Mortality was slightly higher among treated animals (7/15 versus 2/12, p = 0.3). The index of inflammation (0.6 +/- 0.5 versus 0.7 +/- 0.5) necrosis and scarring (0.4 +/- 0.5 versus 0.3 +/- 0.5) among treated and control animals, respectively, was not significantly different, but the size of involved myocardium (149742 +/- 201982 versus 35300 +/- 45413 microns2) was remarkably larger (p less than 0.05), and focal ventricular thinning (5/12 versus 0/10, p = 0.03) was encountered among indomethacin recipients exclusively. These findings indicate that indomethacin treatment in the late phase of coxsackievirus B4 myocarditis enhances myocardial damage and increases the incidence of focal ventricular thinning.

Animals

Synergy between carbenicillin and an aminoglycoside (gentamicin or tobramycin) against Pseudomonas aeruginosa isolated from patients with endocarditis and sensitivity of isolates to normal human serum.

Isolates from the blood of 30 patients with endocarditis due to Pseudomonas aeruginosa were tested for synergy between carbenicillin and an aminoglycoside, either gentamicin or tobramycin, by in vitro checkerboard methods in modified (cation-supplemented) Mueller-Hinton broth. Twenty-five of the 30 isolates were affected synergistically. Whether given low (2.5--5 mg/kg) or high (8 mg/kg) doses of aminoglycoside along with 30 g of carbenicillin daily, all of the five patients infected with pseudomonads that were not synergistically affected were refractory to treatment with pseudomonads that were not synergistically affected were refractory to treatment with the carbenicillin-gentamicin combination, whereas the finding of synergy of carbenicillin with gentamicin (or tobramycin) did not assure a medical cure. Tests for synergy between carbenicillin and gentamicin yielded different results in Mueller-Hinton agar than in modified Mueller-Hinton broth. The majority (28) of 30 isolates of endocarditis-producing P. aeruginosa were resistant to the bactericidal effects of 50% pooled normal serum that had been freshly separated. One of the endocarditis-producing strains that was sensitive to 50% serum was resistant to 10% serum. However, sensitivity or resistance to freshly separated, pooled normal human serum did not predict the outcome of antibacterial therapy for pseudomonas endocarditis.

Aminoglycosides

Delayed type hypersensitivity to allogeneic cells in mice. I. Requirements for optimal sensitization and definition of the response.

Mice were sensitized to allogeneic cells under defined conditions, and their response to antigen deposition in the ear was measured by the influx of radioisotope-labeled cells. The delayed onset, T cell dependency and histology of the ear reaction were characteristic of delayed type hypersensitivity (DTH). Positive responses were obtained in a strain combination unable to elicit a mixed lymphocyte reaction (MLR), in B-Ly mice incapable of cytotoxic T lymphocyte (CTL) generation and in allogeneic combinations challenged with noncellular material. This suggests that MLR and CTL cannot, on their own, account for the response. Hence the ear reaction can best be explained in terms of DTH.

Animals

Delayed type hypersensitivity to allogeneic cells in mice. II. Cell transfer studies.

Sensitivity to allogeneic cell surface antigens was transferred to naive mice by lymphoid cells from sensitized mice. Sensitivity was detected 24-48 h after antigen challenge and was associated with a mononuclear cell infiltration. The cells responsible for transfer were T lymphocytes as demonstrated by successful transfer with cell suspensions enriched for T lymphocytes, and by abrogation of transfer following treatment with anti-Thy-1.2 serum and complement. Both Lyl+ and Ly2+3+ bearing T cells were involved. Removal of Ia+ cells had no effect on the ability of sensitized lymphoid cells to transfer the reaction to naive mice.

Animals

The role of sulfhydryl groups in thyrotropin binding and adenylate cyclase activities of thyroid plasma membranes.

The effects of sulfhydryl (SH) reagents on the binding of TSH to thyroid membranes and on membrane adenylate cyclase activity were studied. Diamide, a SH-oxidizing agent, enhanced [125I]iodo-TSH binding to thyroid membranes in a dose-dependent manner. On the contrary, dithiothreitol (DTT), a disulfide-reducing reagent, markedly inhibited this activity in a dose-dependent manner. These effects could not be attributed to a direct interaction between the reagents and the radioactive TSH. Scatchard plot analysis of the data was limited by curvilinear plots but suggested that diamide increases while DTT decreases the affinity of the receptors for TSH in thyroid membranes, neither reagent appeared to influence the capacity of TSH binding by membranes. The effects of diamide and DTT on adenylate cyclase activity of thyroid plasma membranes were just the opposite of their effects on TSH binding. Thus, diamide inhibited adenylate cyclase activity of thyroid plasma membranes while DTT increased basal enzyme activity and slightly but not significantly increased TSH-stimulated enzyme activity. The data suggest a possible physiological role for SH and disulfide groups of thyroid membranes in modulation of thyroidal activity.

Adenylyl Cyclases

Phase II evaluation of hexamethylmelamine in advanced breast cancer: a Southwest Oncology Group study.

Ninety-eight patients with metastatic breast cancer, heavily pretreated with other agents, were entered in a phase II trial of hexamethylmelamine (HEX). Patients were randomized to receive HEX alone or combined with prophylactic pyridoxine. There was a 2% response rate in 89 partially or fully evaluable patients. Seven percent of these patients developed neurologic toxicity which occurred in the HEX-alone group only.

Aged

Effect of intra-arterial injection of crude cholera enterotoxin on canine small bowel.

Injection of a crude preparation of cholera enterotoxin into the superior mesenteric artery caused isotonic fluid secretion by the canine small bowel. In dogs previously exposed to cellular antigens of Vibrio cholerae, the time course of the intestinal response to intra-arterial injection of crude enterotoxin was similar to that observed after intraluminal exterotoxin challenge.

Animals

Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study.

Patients with advanced breast cancer who had not previously received chemotherapy were treated on a three-arm prospective study: adriamycin day 1 plus 5-FU on day 1 and 8 (AF), adriamycin day 1, plus 5-FU day 1 and 8, and cyclophosphamide day 1 (AFC), and adriamycin day 1 plus 5-FU day 1 and 8, cyclophosphamide day 1 and methotrexate day 1 (AFCM). These courses were repeated every 21 days. The response rate was 44/105 (42%) AF, 44/103 (43%) AFC and 52/105 (49%) AFCM. The length of response was 22, 33 and 35 weeks, respectively, for AF, AFC and AFCM (P = 0.21). The median survival, 64 weeks, was equal in all three limbs. The major toxicity was leukopenia. Twenty-eight percent developed a WBC of less than 2,000/microliter, which resulted in seven deaths (2.2%).

Adult

Implementation of a pneumatic-tube system for transport of blood specimens.

Whole-blood specimens were transported through an installed 485-meter pneumatic-tube system dedicated to blood transport. The system featured constant-speed, low-carrier-velocity travel (3.6 m/sec) with controlled deceleration prior to arrival at its destination. Inserts were designed with ample use of padding to minimize agitation during transport and landing. Serum potassium, hemoglobin, and lactate dehydrogenase activity and whole-blood pH, PCO2, and PO2 were not altered in freshly drawn blood transported in this system. Partial filling or heparinization of the specimen containers did not alter the results. When specimens were allowed to clot prior to pneumatic-tube transport, significantly higher levels of serum lactate dehydrogenase were obtained. This study demonstrates that transport of whole-blood specimens by pneumatic tube without damage to blood components is feasible.

Air

Arginine vasopressin response to an osmotic stimulus in the fetal sheep.

Baseline plasma osmolality (pOsm) and plasma arginine vasopressin (pAVP) were measured in chronically catheterized fetal sheep. Mean baseline pAVP in fetuses from 101-120 days was 1.9 +/- 0.46 muU/ml (mean +/- SEM) with a pOsm of 293 +/- 1.8 mOsm/kg. In fetuses of 121-141 days of gestation, mean pAVP was significantly lower, 0.77 +/- 0.19 muU/ml (P less than 0.05), with a similar pOsm (293 +/- 1.9 mOsm/kg). The logarithmic baseline pAVP values were linearly correlated with pOsm for both groups. Hypertonic saline infusion resulted in a similar increase in the log pAVP corrected for the rise in pOsm in the 101-120-day fetuses and in 121-141-day fetuses. The slope of this response was similar to that of the steady state relationship. The data indicates that the fetal osmoreceptor system for control of arginine vasopressin secretion is fully functional in the last trimester of pregnancy.

Animals

Cyanide toxicity following nitroprusside induced hypotension.

Several recently reported deaths following the use of sodium nitroprusside have been attributed to the accumulation of the nitroprusside metabolite, cyanide. In this study, brief nitroprusside infusions (mean = 36 minutes) were administered in currently recommended doses during intracranial surgery. The peak blood cyanide following the infusions was 65.2 +/- 17.5 microgram per cent (mean +/- SE) (n = 13). It occurred within 45 minutes after infusion. The highest cyanide level detected was 205 microgram per cent, which is within the range of reported lethal blood cyanide levels. Metabolic acidosis developed in the four patients with the highest blood cyanide levels (range 90-205 microgram per cent). This occurred between 45 and 180 minutes following the cyanide peak. Blood ATP levels were depressed in the same patients. These findings are indicative of disturbed aerobic metabolism. We conclude that there is evidence of cyanide toxicity when nitroprusside is infused into patients using currently recommended doses. We recommend that for short infusions the dose of sodium nitroprusside should not exceed 0.5 mg/kg.

Acidosis

The influence of lead strength on the S-T changes with exercise electrocardiography (correlative study with coronary arteriography).

The contribution of relative lead strength to S-T segment depression amplitude during exercise was evaluated in 98 patients who had both a treadmill stress test and a coronary arteriogram. This was accomplished by constructing an exercise S-T depression to R wave ratio (S-T/R) and then relating these ratios to the extent of coronary disease found with arteriography. The additional criterion of 1 mm S-T depression for the bipolar V5 and 0.5 mm for the late unipolar V5 was also reviewed. These criteria were then compared to the sensitivity and specificity of the usual 1 mm S-T depression criterion. The S-T/R ratio of 0.04 improved the detection of significant coronary disease over the usual criteria. The ratio of 0.1 was effective in avoiding false positive tests but lacked sensitivity. This would suggest that strong lead systems may give false positive S-T changes with exercise. The use of 0.5 mm depression as abnormal for the post-exercise unipolar V5 improved sensitivity without loss of specificity over the usual criteria of 1 mm S-T depression criteria. This may be a reflection of the voltage differences between the bipolar lead and the unipolar lead in these two lead systems. It is concluded that lead strength must be considered when evaluating the S-T response to exercise.

Angina Pectoris

A further example of Kp1/Ko exhibiting depression of some Kell group antigens.

This paper gives details of a family in which there are numerous examples of the heterozygous Kdegree state. The study was initiated by the presence of anti-Kpb in the serum of the propositus. Reactions with anti-K, anti-Ku, anti-Jsb and anti-K13 confirm that the Kdegree gene in trans with Kpa results in weaker expression of these Kell antigens. One example of anti-K showed some evidence of dosage effect with kKpb/Kdegree cells, but these results were not confirmed by quantitation studies.

Blood Group Antigens

Dopaminergic function in two patients with catalepsy.

Apomorphine HC1 (2 mg subcutaneously), a dopamine receptor agonist, was administered to two schizophrenic patients with catalepsy. In one of these patients the clinical response to apomorphine was compared with that of sodium amytal and the growth hormone response apomorphine (0.75 mg subcutaneously) was compared with that of 25 control subjects. Apomorphine had no effect whereas sodium amytal caused rapid disappearance of catatonic symptoms including catalepsy. The peak growth hormone response to apomorphine was similar to that of controls. These data suggest that unlike experimental catalepsy in animals, catalepsy associated with schizophrenia may not be dependent on impaired dopaminergic function. Further case studies as well as the use of other dopamine receptor agonists are required before definite conclusions can be drawn.

Adult