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Biomedical subjects

C Johnston

Publications and source records attributed to C Johnston.

At least 199 records · Page 11Linked to original sources

Induction chemotherapy followed by radical surgery in cervical cancer.

To evaluate the therapeutic potential of cytotoxic therapy in patients with squamous cell carcinoma of the cervix, 28 patients with disease clinically localized to the pelvis were treated with chemotherapy followed by radical pelvic surgery. Treatment consisted of cis-platinum 50 mg/m2, mitomycin C 10 mg/m2, vincristine 1.0 mg/m2, and bleomycin 10 U IM given as a course (over 21 days) of induction chemotherapy followed by radical hysterectomy and pelvic and aortic lymphadenectomy in 26 patients and total pelvic exenteration in 2 patients. The stage distribution of the patients in the study was 4 stage IB, 6 stage IIA, 7 stage IIB, 1 stage IIIA, 11 stage IIIB, and 1 stage IVA. Two patients with stage IIIB cancer were found, at the time of laparotomy, to have carcinomatosis and were excluded from the final evaluation in this study. All patients achieved a clinical and histologic response to chemotherapy. There were 35% complete and 65% partial responses. After chemotherapy, at the time of surgery, 4 patients were found to be histologically free of disease, and the incidence of surgically documented nodal disease after chemotherapy was found to be 32%. There was no significant hematologic or pulmonary toxicity. Induction chemotherapy is well tolerated and may be beneficial in the management of some patients with cervical cancer who are at high risk for failure with conventional treatment.

Adult↗

Temperature relationship to distance and flow rate of warmed i.v. fluids.

STUDY OBJECTIVE: To determine whether therapeutic benefit is obtained by administering warmed IV fluid to hypothermic children. DESIGN: Saline at 37 C in standard IV tubing was subjected to temperature measurements within a fluid warmer and at 5, 25, 45, 65, 85, and 105 cm distally. Flow rates varied from 20 to 1,000 mL/hr. SETTING: The Children's Hospital of Alabama emergency department. TYPE OF PARTICIPANTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Temperature readings were made every minute until the volume required to flush the tubing had infused. Only at rates of 750 and 1,000 mL/hr did the fluid remain warmer than 32 C more than 25 cm from the warmer. CONCLUSION: At flow rates usual in pediatrics, hypothermic patients must be connected to fluid warmers by lengths of IV tubing shorter than customary or practical in the ED to benefit from this treatment modality.

Child↗

Preoperative silent myocardial ischaemia: incidence and predictors in a general surgical population.

We have studied before operation 156 patients aged more than 40 yr presenting for elective vascular or non-vascular surgery, using ambulatory ECG monitoring to detect silent myocardial ischaemia (SMI). The prevalence of SMI was 18.2% in the vascular group (n = 102) and 7.6% in the non-vascular group (n = 54). A history of ischaemic heart disease, or an abnormal ECG suggestive of a previous myocardial infarction, predicted a high risk of SMI (28% compared with 9% in the absence of these variables). However, a significant amount of SMI (36% of the total) occurred in patients without one of the defined risk factors. In addition, 24 of the patients with abdominal aortic disease underwent cardiac gated blood pool (MUGA) scans. Abnormal ventricular wall function was observed in 62.5% of the patients. Twenty-nine percent of the patients studied with MUGA scans had SMI and 21% had ejection fractions less than 40%. A significant association (P less than 0.05) existed between the presence of SMI and a ventricular ejection fraction of less than 40%.

Adult↗

Angiotensin-converting enzyme in macro- and microvessels of the rat.

1. Angiotensin-converting enzyme (ACE) was measured in the aorta, cerebral and mesenteric microvessels of Wistar-Kyoto rats using a specific radioligand assay. 2. Ligand binding studies revealed a four-fold increase in concentration of ACE in mesenteric microvessels, compared with aorta or brain microvessels. The dissociation constant (Kd) was similar in all tissues. 3. The effects of oral administration of the ACE inhibitor S9650 on vascular ACE in vivo were measured. 4. S9650 produced a dose-dependent inhibition of vascular ACE from brain and mesenteric microvessels.

Angiotensin-Converting Enzyme Inhibitors↗

4-Hydroperoxycyclophosphamide purging of breast cancer from the mononuclear cell fraction of bone marrow in patients receiving high-dose chemotherapy and autologous marrow support: a phase I trial.

We designed an ex vivo bone marrow treatment for breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support (ABMS), using 4-hydroperoxycyclophosphamide (4-HC), an active derivative of cyclophosphamide with known activity against breast cancer. This phase I bone marrow purging trial used ficoll-separated mononuclear cells (MNC) (devoid of granulocytes and RBCs), as opposed to the buffy coat. Twenty-five patients with metastatic breast cancer were studied. Patients received three cycles of the Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), fluorouracil, and methotrexate (Duke AFM) regimen, followed by marrow harvest. An MNC fraction of marrow was prepared and treated with 4-HC in concentrations of 20 micrograms/mL (four patients), 40 micrograms/mL (four patients), 60 micrograms/mL (nine patients), or 80 micrograms/mL (eight patients) and cryopreserved. Patients then received high-dose systemic cyclophosphamide, cisplatin, and carmustine, followed by infusion of the purged marrow. The study end point was marrow engraftment, defined as WBC count greater than 1,000 cells per microliter. At the first three dose levels (20, 40, and 60 micrograms/mL 4-HC), there was no significant delay in time to engraftment (19, 20, and 23 days, respectively) compared with the unpurged historical controls (17 days). At 80 micrograms/mL, engraftment was significantly delayed compared with the lower concentrations (P = .027), and further escalation of 4-HC was not attempted. A significant correlation was observed between the time of leukocyte engraftment and the 4-HC concentration (P = .017). With a methylcellulose-based tissue culture assay, we demonstrated a statistically significant correlation between the colony-forming unit-granulocyte-macrophage (CFU-GM) content in the purged marrow and the days to engraftment. Ninety-five percent of patients responded clinically to the entire program, 55% of them completely. Longer follow-up is required to assess the ultimate benefit of intensive therapy on long-term survival.

Adult↗

Specificity, sensitivity and diagnostic predictive value of selected laboratory generated autoantibody profiles in patients with connective tissue diseases.

We tested the hypothesis that the application of 5 laboratory generated serologic profiles facilitates the interpretation of individual autoantibodies in connective tissue diseases without loss of specificity, sensitivity or diagnostic predictive value. The predetermined laboratory generated autoantibody profiles were analyzed in 423 sera from patients with clinically diagnosed connective tissue diseases. All sera positive for one or more autoantibodies to a selected panel of nuclear antigens could be segregated into one of 5 profiles. The distribution of individual autoantibodies and profiles in the sera of patients with various connective tissue diseases were compared in terms of their respective diagnostic predictive value and sensitivity. The application of these profiles improved the sensitivity and diagnostic predictive value of these tests when compared to individual autoantibodies without loss of specificity, thus aiding clinical interpretation.

Antibody Specificity↗

Immunomagnetic purging of breast cancer from bone marrow for autologous transplantation.

Intensive chemotherapy with autologous bone marrow transplantation is a promising approach for the treatment of breast cancer, provided that clonogenic tumor cells do not contaminate the patient's bone marrow. We have previously demonstrated that a combination of 4-hydroperoxycyclophosphamide (4-HC) and immunomagnetic purging (IMP) with monoclonal antibodies and microspheres could remove 4-5 logs of clonogenic breast cancer cells from a 10-fold excess of human bone marrow cells. In the present report we have evaluated an apparatus for separating tumor cells from a large volume of human marrow. This apparatus will permit preparation of large volumes of purged marrow for use in studies of intensive therapy with autologous marrow support. Bone marrow progenitor cell (CFU-GM) recovery following this IMP technique was 85% of the unpurged control, and suggests that marrow recovery following high dose systemic chemotherapy will not be adversely affected. A phase I study to evaluate marrow reconstitution following IMP is underway. Preliminary data suggest that this IMP method will not delay engraftment in breast cancer patients receiving high-dose chemotherapy and autologous bone marrow support, but further study is required.

Adenocarcinoma↗

Maternal characteristics, ratings of child behavior, and mother-child interactions in families of children with externalizing disorders.

Relationships among maternal characteristics, ratings of child behavior, and observed mother-child interactions were examined in a sample of 40 4- to 12-year-old children with externalizing disorders. Mothers and children were observed in a task interaction and mothers provided self-reports of depressed mood, parenting self-esteem, marital satisfaction, social support, and life stress. Child behavior was rated by both mothers and teachers. Several significant correlations were found among observed mother and child behaviors and among maternal self-report measures. However, few significant relationships were found between maternal characteristics and observed mother or child behavior. Although life stress predicted increased child negativity, maternal depressed mood was related to more appropriate child behavior. Mother and teacher ratings of child behavior demonstrated few significant relationships with other measures. These results suggest that, in samples comprised primarily of children with attention deficit disorder from socially advantaged families, few relationships exist between maternal characteristics, parenting behavior, and child behavior.

Adult↗

Preoperative parental anxiety predicts behavioural and emotional responses to induction of anaesthesia in children.

Parental presence at induction of anaesthesia is desirable if it makes the child happier and more cooperative. This study evaluated the emotional and behavioural responses of children to being accompanied by a parent at induction of anaesthesia in a paediatric day-care surgical centre. One hundred and thirty-four patients (aged 2-10 yr, ASA physical status I or II) were divided into two groups by day of surgery, to have a parent present at induction of anaesthesia (treatment group), or to be unaccompanied (control group). Before, and at one week after surgery, the child's fears and behaviour were scored by the Hospital Fears Inventory (HFI) and Behavioural Questionnaire (BQ), and parental anxiety by the Parents' Questionnaire (PQ) before and at one week after surgery. The Global Mood Scale (GMS) was used to assess the child's behaviour and the Visual Analogue Scale (VAS) to assess the parent's anxiety on arrival for surgery and at induction of anaesthesia. All patients and parents were disturbed by the experience, but to the same degree in the treatment and control groups. Subgroups of "calm" and "anxious" parents were identified by a median split of their preoperative VAS scores. Children in the "calm-treatment," "calm-control" and "anxious-control" subgroups were similarly upset at induction. Children in the "anxious-treatment" subgroup were the most disturbed at induction, and significantly more than those in the "anxious-control" subgroup. Preoperative parental anxiety levels also correlated with the child's fears and behaviour one week after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Serotonin involvement in analgesia induced by transcranial electrostimulation.

The experiments described here were intended to investigate whether serotonin (5HT) may be involved in analgesia induced by low current transcranial electrostimulation (TE). The TE stimulus is a 10 mu-ampere, 10 Hz, pulsed current transmitted via electrodes in the pinnae. Combinations of the following were given as intraperitoneal injections: 300 mg/kg p-chlorophenylalanine (pCPA) 48 hours before testing, 100 mg/kg 5-hydroxytryptophan (5HTP) 30 min before testing and the saline vehicle for these drugs. Rats were tested prior to and 30 minutes after TE or sham TE. Testing for analgesia consisted of putting progressively increasing pressure on the rat tail 1/4 inch from the tip with a pneumatically driven, right angle wedge. The amount of pressure at which the rat moved its tail was measured both before and after TE, or sham TE, and recorded as the difference in tolerated peak pressure (DTPP). TE produced analgesia as manifested by a 613 percent increase in DTPP compared with sham TE treatment values. Among TE treated rats, pretreatment with pCPA decreased DTPP 91.5 percent compared with saline control values, indicating 5HT involvement. 5HTP restored TE induced analgesia in pCPA treated rats to the level of saline treated control animals, confirming 5HT involvement.

5-Hydroxytryptophan↗

Critical care interhospital transports: predictability of the need for a pediatrician.

The Children's Hospital of Alabama Critical Care Transport System provides a mobile intensive care unit for interhospital transfer of critically ill pediatric patients. The transport team consists of a pediatrician, a pediatric emergency nurse, and a respiratory therapist. We studied whether it was possible to determine in advance whether it was always necessary for a physician to be on the team. The transport physician made a determination of need for a physician based on data available prior to transport (preassessment). After the transport was completed, the physician made a retrospective determination of actual need for a physician (postassessment). Over a period of eight months, 148 questionnaires were analyzed. In 108 transports (73%), there was minimal or no change in need for a physician between the pre- and posttransport assessments. Therefore, an accurate prediction of need for a physician was possible in advance. Of the remaining transports in which the determination was significantly changed, 37 (25%) indicated a decrease in actual need for a physician after completion of the transport. There was a significant increase over the prediction in the actual need for a physician in only three cases (2%).

Adolescent↗

Islet function and insulin sensitivity in the non-diabetic offspring of conjugal type 2 diabetic patients.

To determine whether the genetic predisposition towards Type 2 diabetes was associated with a defect in either islet-cell function or insulin action, 12 non-diabetic offspring each of whose parents both had Type 2 diabetes were studied, together with 12 control subjects matched for age, sex, and weight. Fasting plasma glucose was higher in the offspring (5.5 +/- 0.1 mmol l-1 (mean +/- SE)) than in the matched controls (5.1 +/- 0.1 mmol l-1) (p less than 0.05). Using an IVGTT insulin sensitivity was not significantly lower in the offspring compared with their controls (3.1 +/- 0.5 vs 3.8 +/- 1.0 min-1 mU-1 l 10(-4)). There was no significant difference in any of the measures of insulin secretion (first- and second-phase response to IV glucose, slope of glucose potentiation, and maximal glucose regulated insulin secretory capacity). Glucagon secretion measured before and after a stimulus of IV arginine at varying plasma glucose concentrations was virtually identical in the offspring and their controls. Among a total of 28 non-diabetic subjects of differing body-weights there was a significant inverse relationship between insulin sensitivity and insulin secretion. When adjusted for their generally lower insulin sensitivity, maximal insulin secretory capacity was reduced in the offspring (p = 0.038, one-tailed t-test). The results suggest that the genetic predisposition to Type 2 diabetes is not associated in young adults with any major pre-morbid impairment in insulin secretion or insulin action but the relationship between the two may be abnormal. Islet A-cell function appears to be normal.

Adult↗

Are thyrogastric autoantibodies associated with an increased susceptibility to developing type 1 (insulin-dependent) diabetes? A study in identical twins.

To examine whether the presence of thyrogastric autoantibodies is associated with an increased susceptibility towards developing type 1 diabetes we have tested for thyroid (microsomal and thyroglobulin) and gastric-parietal cell antibodies in 86 pairs of identical twins, 47 discordant and 39 concordant for type 1 diabetes. Autoantibodies were detected in both twins of a pair in 35 and in neither twin in 45 pairs. In only 6 pairs (3 discordant) was there a discrepancy in the antibody results between co-twins. The frequency of antibodies was similar in twin pairs discordant, (21/44, 48%), and concordant, (14/36, 39%), for diabetes. Thyrogastric antibodies were not more frequent in pairs that were female, diagnosed above the age of 20, or had HLA DR3 as opposed to DR4. We conclude that thyrogastric autoantibodies are common in both type 1 diabetic patients and their non-diabetic identical twins. Their presence appears to be genetically determined but does not increase the susceptibility of developing diabetes. The presence of autoantibodies does not appear to indicate a separate aetiological type of diabetes.

Autoantibodies↗