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Biomedical subjects

K S Hall

Publications and source records attributed to K S Hall.

At least 55 records · Page 3Linked to original sources

The synthetic hepatic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibit growth of MH1C1 rat hepatoma cells transplanted into Buffalo rats or athymic mice.

Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH1C1 rat hepatoma cells by 50-70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tumor growth in athymic mice. The amide free peptide pyroglutamylglutamylglycylserylaspartic acid which inhibited the tumor growth in all the models showed a curvilinear dose-response relationship with a maximal effect at 1000 pmol/animal in mice and at 100 pmol/animal in rats. The amidated peptide pyroglutamylglutamylglycylserylasparagine, which was only tested in the lung model, showed growth inhibition with 2, 20, or 200 pmol/animal, but 200 pmol/animal was most effective. We have recently reported that these peptides show cochromatography with hepatic growth inhibitory peptides, isolated from mouse liver.

Animals↗

Base deficit stratifies mortality and determines therapy.

OBJECTIVE: To determine the association of base deficit with mortality and other factors affecting mortality. DESIGN: Retrospective review. SETTING: Tertiary care center. PARTICIPANTS: Consecutive samples of 3791 trauma patients admitted with an arterial blood gas sample taken in the first 24 hours. MAIN OUTCOME MEASURES: Age, injury mechanism, head injury, shock (systolic blood pressure less than 90 mm Hg), Revised Trauma Score, TRISS probability of survival Ps, and mortality. RESULTS: Most (3038) patients (80.1%) exhibited a base deficit. Base deficit, age, injury mechanism, and head injury were associated with mortality using logistic regression. Age less than 55 years, no head injury, and a base deficit of -15 mmol/L were associated with 25% mortality. Age greater than or equal to 55 years with no head injury or age less than 55 years with a head injury and a base deficit of -8 mmol/L were associated with a 25% mortality. When shock was added to the model, all factors remained significant, and base deficit was supplemental to blood pressure. Base deficit also added significantly to the Revised Trauma Score and TRISS measurements. CONCLUSIONS: The base deficit is an expedient and sensitive measure of both the degree and the duration of inadequate perfusion. It is useful as a clinical tool and enhances the predictive ability of both the Revised Trauma Score and TRISS.

Academic Medical Centers↗

Cross-cultural studies in Alzheimer's disease.

The search for risk factors for Alzheimer's disease would be greatly enhanced by identification of populations with significantly different prevalence rates, particularly if these populations consisted of ethnic groups now living in different environments and cultures. Evidence is presented that two such groups are worthy of further study: subjects of African origin living in Africa and in the West and Native Americans living on and off reserves.

Black or African American↗

Long-term toxicity of preoperative 4'-epidoxorubicin (Epi-adriamycin) in partially hepatectomized rats.

4'-Epidoxorubicin (Epi-A) administered immediately prior to liver resection has been suggested as treatment for patients with primary liver carcinoma. Long-term toxicity was studied in rats given a single dose of Epi-A intravenously immediately prior to a standard partial hepatectomy (PH). After 52 weeks only 9% of the rats given 5 mg/kg + PH were alive, 79% of the rats given 2 mg/kg + PH and 92% of the PH control survived. The weight gain of the rats given 5 mg/kg + PH was only 17% of that of PH controls. Signs of congestive heart failure were observed in some rats while in others moderate kidney lesions. No histopathological lesions were detected by light microscopy in heart, liver, spleen and bone marrow. For the rats given 2 mg/kg + PH body weight gain, microscopic observations and blood chemistry data (total protein, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin, creatinine and urea) were comparable to the PH controls. No significant differences in survival were registered between partially hepatectomized and sham-operated rats. The results indicate that Epi-A may be given preoperatively to liver resection without inducing long-term effects on vital organs.

Animals↗

The influence of partial hepatectomy on the pharmacokinetics of preoperatively injected 4'-epidoxorubicin in rats.

Preoperative administration of 4'-epidoxorubicin (Epi-A) has been suggested as adjuvant therapy in patients undergoing liver resection for hepatocarcinoma. To assess the influence of partial hepatectomy on the pharmacokinetics of Epi-A, an experimental study in rats was undertaken in which 5 mg/kg Epi-A was given i.v. 10 min prior to a 2/3 hepatic resection or sham operation. Epi-A levels in liver tissue and plasma were determined using a sensitive and specific HPLC method. A marked uptake of Epi-A in liver tissue was found at 10 min after injection. The partially hepatectomized rats showed a 2-fold increase in AUC between 4 and 72 h as compared with the sham-operated controls. The terminal half-life from 24 to 72 h was not significantly changed by the partial hepatectomy. The plasma binding of Epi-A was measured at 4 h post-surgery. The fraction of unbound Epi-A was 0.16 in partially hepatectomized animals and 0.20 in sham-operated rats. The results indicate that when Epi-A is given prior to liver resection, a dose reduction might be necessary to avoid increased side effects due to the rise in AUC.

Animals↗

Verapamil potentiates 4'-epidoxorubicin cytotoxicity in a rat hepatoma cell line and in a substrain resistant to 4'-epidoxorubicin.

We have examined the influence of verapamil (VP) on the in vitro effect of 4'-epidoxorubicin (Epi-A) in a rat hepatocarcinoma cell line (MHlCl) and in an Epi-A resistant substrain. A VP concentration of 500 ng/ml (1.1 mumol/l) markedly potentiated the cytotoxic effect of Epi-A in the parent line. The resistant cells grow at an Epi-A concentration of 7500 ng/ml (12.9 mumol/l). This is approximately 15-fold higher than the concentration tolerated by parental cells. In these cells VP reversed the acquired resistance to Epi-A in a concentration dependent manner; thus, a concentration in the range of 500-750 ng/ml (1.1-1.7 mumol/l) of VP restored the sensitivity to Epi-A in the resistant cells. Our results demonstrate that VP increases the sensitivity to Epi-A in hepatocarcinoma cells never exposed to this drug, as well as in hepatocarcinoma cells with acquired Epi-A resistance.

Animals↗

Alkaline induction of a novel gene locus, alx, in Escherichia coli.

A novel pH-regulated locus inducible over 100-fold in alkaline media was identified in Escherichia coli through screening of 93,000 Mu dI1734 (lacZ Kmr) operon fusions at pH 6.5 and pH 8.5. Four lacZ fusions that showed expression only at the higher pH were mapped at 67.5 min by P1 transduction crosses. The locus was designated alx.

Crosses, Genetic↗

Effect of preoperative 4'-epidoxorubicin (epi-adriamycin) treatment on the regeneration and function of the liver in partially hepatectomized rats.

The early effects of 4'-epidoxorubicin (Epi-Adriamycin) on liver regeneration and late effects on liver function were studied after a standard partial hepatectomy in rats. 4'-epidoxorubicin was given intravenously immediately preoperatively. Neither suppression nor delay in DNA synthesis (analyzed by incorporation of 3H-thymidine) during the first 72 h postoperatively was registered after a dose of 5 mg/kg body weight. Four weeks following the dose of 5 mg/kg a slight decrease was found in liver weight (8%), body weight (8%) and plasma albumin values (9%) compared with the partial hepatectomized controls. Total protein, alkaline phosphatase, total bilirubin and alanine aminotransferase were not changed. A dose of 2 mg/kg did not alter any of the parameters. No histological signs of liver and kidney damage were seen. The results indicate that preoperative treatment with 4'-epidoxorubicin combined with partial hepatectomy may possibly be used in humans without clinically significant impairment of liver regeneration and function of the remaining liver and without histological detectable nephrotoxicity. The dosage of 4'-epidoxorubicin must, however, be adjusted according to species differences in pharmacokinetics.

Animals↗

Intelligent computer-based assessment and psychotherapy. An expert system for sexual dysfunction.

New and converging developments in the areas of artificial intelligence, intelligent tutoring systems, and cognitive therapy have made possible a new approach to computer-assisted assessment and psychotherapy. This new approach combines the capacity for intelligent therapeutic dialogue with the presentation of individualized therapeutic interventions. Previous attempts at computerized psychotherapy are reviewed to highlight a newly developed rule-based expert system, Sexpert, which assesses and treats sexual dysfunction. Preliminary observations concerning couples' reaction to and acceptance of Sexpert are presented.

Artificial Intelligence↗

The CAMDEX: a standardized instrument for the diagnosis of mental disorder in the elderly: a replication with a US sample.

The Cambridge Mental Disorders of the Elderly Examination (CAMDEX) was developed by Roth, et al (1986) to assist in the early diagnosis and measurement of dementia in the elderly. In this study the CAMDEX was administered to a mixed group of independently diagnosed elderly psychiatric patients and control subjects in the United States. The CAMDEX was found to have a high interrater reliability with a mixed group of clinicians of varying backgrounds. The diagnostic scales and the cognitive section of the CAMDEX demonstrated considerable promise in distinguishing between independently diagnosed populations of depressed, demented, and normal subjects. The results suggest comparability between samples of subjects in England and the US, and that the CAMDEX is a promising instrument for use in both research and clinical settings.

Aged↗

Cancer of the penis. Experience at the Norwegian Radium Hospital 1974-1985.

The cancer-related 5-year survival was 80% in 79 patients with penile cancer treated at the Norwegian Radium Hospital from 1974 to 1985 (N0 = 61, N1-2 = 12, N3 = 6). Sentinel node biopsy (SLN) of the inguinal lymph nodes medial to the saphenous vein helps to identify patients with early regional spread. The survival for these N+ patients is favourable if radical lymph node dissection is performed immediately. A tumour-negative SLN biopsy does, however, not exclude the subsequent development of inguinal lymph node metastases. These were found equally often during follow-up in patients with or without primary performance of SLN biopsy. Five of 6 patients, relapsing with groin metastases, were cured by secondary lymph node dissection. Most of the small primary tumours (T1/T2) can be treated radically by primary radiotherapy, but frequent follow-up is necessary to detect surgically curable penile recurrences (3 of 11 patients). Combination treatment of chemotherapy, radiotherapy and surgery represents a good palliation treatment in advanced cases.

Adult↗

Resonance Raman studies of isotopically labeled chloroperoxidase.

Chloroperoxidase (CPO) and cytochrome P450cam have been shown by several techniques to have similar active site properties. Recent resonance Raman investigations using isotopically enriched 34S-labeled samples have demonstrated thiolate ligation in the P450cam system. We report here on a number of parallel studies involving CPO. On the basis of isotopic labeling (34S, 13CO), we assign the Fe-S and Fe-CO stretching frequencies of CPO at 347 (-vFe-S) and 488 cm-1 (-vFe-CO). The differences of the -vFe-S and -vFe-CO in CPO and P450cam may suggest subtle differences in the thiolate binding in the two systems.

Chloride Peroxidase↗

High-dose cis-platinum combination chemotherapy in advanced nonseminomatous malignant germ cell tumours with emphasis on nephrotoxicity.

High-dose cis-platinum treatment (180 mg/m2 per cycle) in combination with VP16 and bleomycin was given to 14 patients with highly advanced nonseminomatous malignant germ cell tumours (total: 31 cycles). Cis-platinum was administered in infusions of 0.9% NaCl given daily for 3 days with 3-week intervals. An intensive hydration regimen (71 NaCl/day) provided a urinary output of at least 1000 ml/4 h. The response and side effects were evaluated. Ultimately 11 of 12 patients evaluable for treatment effect were rendered tumour-free and are alive with NED. All 14 patients were evaluable for toxicity; 2 developed life-threatening lung edema during the initial prehydration period and did not continue the high-dose cis-platinum schedule. After one to four cycles of high-dose cis-platinum treatment the 131I-Hippuran clearance was reduced by 28%. Decreased kidney function evaluated by 131I-Hippuran clearance was the reason for discontinuation of treatment in 5 patients. Patients with ureteric obstruction represented a high-risk group for reduction of kidney function. High-dose cis-platinum therapy is an intensive treatment demanding a high level of investment of resources, which has promising response rates in patients with highly advanced malignant germ cell tumours. Short-term clinically significant reduction of the kidney function can be avoided by intensive hydration of the patient.

Adolescent↗

Stability of the postpsychotic depression syndrome.

Fifteen consecutively identified patients with syndromally defined postpsychotic depression were followed prospectively over three consecutive weekly ratings to assess the stability of that syndrome. In 8 cases, the condition persisted with undiminished intensity. Five cases remitted spontaneously, and in 2 cases the syndrome appeared to be a harbinger of psychotic relapse. The implications for the timing of therapeutic interventions in patients with postpsychotic depressions are discussed.

Adult↗

Estimating odds ratios adjusting for misclassification in Alzheimer's disease risk factor assessment.

Epidemiological studies of Alzheimer's disease and dementia are often two-phase studies including a screening phase and a clinical assessment phase. It is common to interview a relative of the subject at each of these phases to obtain information about the subject's exposure to risk factors. This can result in a misclassification error when assessing risk factors, as the two responses of the relative often differ. This is especially a problem for risk factors involving life-style and family history which cannot be confirmed using the subject's medical records. A naive analysis using data from each phase separately would give two different estimates of the odds ratio; both estimates could be biased. In this paper, we extend the estimation methods adjusting for misclassification developed by Liu and Liang to data collected through two-phase sampling. We first use a latent class analysis and the EM algorithm to estimate the misclassification parameters. We then derive the maximum pseudo-likelihood estimators, conditional on the misclassification parameters, to estimate the odds ratios accounting for the complex sampling study design. We propose to use the jack-knife estimator for estimation of the variances. We apply the above method to data collected in the Indianapolis-Ibadan Dementia Study to estimate the odds ratio for smoking adjusting for misclassification error.

Black or African American↗