Biomedical subjects
Publications and source records attributed to J Hannah.
We describe 2 cases of extrarenal angiomyolipoma of the perinephric space. All other cases of extrarenal angiomyolipoma of the retroperitoneum are reviewed and the clinical relevance of this unusual pathological entity is discussed.
To investigate the role of plasma insulin on food intake, we have examined the effect of naturally occurring chronic hyperinsulinemia on the feeding behavior of male rhesus monkeys. Two groups of monkeys, a group with normal fasting insulin concentrations (52.4 +/- 2.2 microU/ml) (mean +/- SE) and a hyperinsulinemic group (148.6 +/- 14.5 microU/ml), were selected to be similar in weight, 13.0 +/- 1.0 and 15.3 +/- 0.5 kg, respectively, prior to study. Food intake and feeding patterns were recorded and analyzed. No differences in either daily caloric intake, 815.2 +/- 27.4 versus 890.0 +/- 64.2 kcal (p less than 0.32), or feeding patterns were found. The number of meals taken per day did not differ between the two groups, 8.7 +/- 1.7 versus 6.7 +/- 1.1 (p less than 0.35), nor did meal size differ, 129 +/- 16.5 versus 110.5 +/- 16.3 (p less than 0.45). We conclude that chronic endogenous hyperinsulinemia as it occurs naturally in some obese rhesus monkeys has no significant effect on daily feeding behavior.
Early endocrine therapy after radical retropubic prostatectomy was compared to radical prostatectomy alone (nonearly endocrine therapy) for the treatment of carcinoma of the prostate with lymph node metastases. Our retrospective analysis demonstrated that the 2 cohorts were similar with respect to patient age, Gleason sum score, seminal vesicle invasion, lymph node involvement, tumor volume and pathological stage of the primary tumor. The cause-specific survival of the entire group was 84% at 60 months and 78% at 98 months. The cause-specific curves for the early and nonearly endocrine therapy group were not significantly different (p less than 0.194), although the estimated 9-year survival rates were 91 and 71%, respectively. Survival free of disease was significantly prolonged in the early endocrine therapy group (p less than 0.030), with a 9-year estimated rate free of disease of 67% versus 32% in the nonearly endocrine therapy group. Followup prostate specific antigen serum levels were analyzed and the value as a progression marker is discussed. These data suggest that a radical operation plus early endocrine therapy is effective palliation in selected patients with low volume lymph node metastases, producing clinical survival free of disease in most patients.
The relationship between histological prognostic indicators and their relative significance in prognosis were studied in 139 patients who underwent radical prostatectomy. The estimated progression rates at 5 and 8 years were 14 and 52% respectively for patients with high grade tumours, 25 and 50% for those with capsular penetration, 31 and 58% for patients with seminal vesicle invasion and 23 and 55% for those with lymph node metastases. Each of the 4 parameters yielded an approximately equal increased risk of disease progression at 5 and 8 years. The occurrence of 2 or more risk factors in the same patient did not result in a statistically increased risk of progression at 5 and 8 years. The effect of capsular involvement on progression was directly related to the extent of invasion. The progression rate at 8 years was 3% for patients with mild involvement, 19% for those with extensive invasion and 50% for those with capsular penetration.
We report the case of a 23-year-old man with a giant-cell tumor of the sphenoid bone. The radiologic manifestations consisted of an expansile mass arising from the sphenoid bone with extension into the cranial cavity and the nasopharynx. The findings with computed tomography and magnetic resonance imaging best reflected respectively the osseous and soft-tissue extent of the disease.
DNA analysis was performed on fresh frozen samples of the primary tumor in 32 patients with renal carcinoma (13 with apparently localized disease and 19 with metastases at presentation). A comparison of ploidy with staging and standard histologic variables was performed. None of the patients who presented without metastases died of disease during the follow-up period. Eleven of 13 patients of this group had a diploid/near diploid pattern, and metastases developed in only one patient. Patients with metastatic disease and a diploid/near diploid DNA content had a significantly better survival rate than those with aneuploid primary tumors. Statistical analysis showed that grade and ploidy contributed significant but independent prognostic information. We concluded that DNA content is a useful prognostic factor in renal carcinoma.
An oncocytic carcinoid of the kidney producing a periodic Cushing's syndrome in an adolescent is described. The tumor displayed gross, histologic, and ultrastructural features similar to renal oncocytoma, another unusual renal neoplasm. A review of renal carcinoids and possible associations between oncocytic change and periodic hormone production are discussed.
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A series of analogues of acyclovir and ganciclovir were prepared in which conformational constraints were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related base-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, (+/-)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a. Another group, typified by (+/-)-9-[[(E)-2-(hydroxymethyl)cyclopropyl]methyl]adenine (17b), possessed modest antiviral activity despite an apparent inability to be enzymatically phosphorylated. The relationship of side-chain conformation and flexibility to biological activity in this series is discussed.
One hundred and nine patients treated by total prostatectomy for apparently localised carcinoma were analysed to investigate the prognostic significance of capsular invasion and penetration, seminal vesicle invasion, lymph node metastases, grade as assessed by the Gleason and MD Anderson Hospital (MDAH) systems and DNA content measured by flow cytometry of nuclear material extracted from paraffin embedded tumour. Comparison of DNA content was made with 36 benign prostates. Mean follow-up/survival was 60.7 months, at which time 21 patients had evidence of recurrence or had died. Only 5 patients had local recurrence. Tumour grade, as assessed by both the Gleason Sum Score and the MDAH system, correlated with anatomical extent and was the most important determinant of time to recurrence. Fifty-nine tumours were diploid, 44 tetraploid and 6 aneuploid. One of 36 benign prostates showed aneuploidy. Ploidy did not correlate with the anatomical extent of the tumour or with grade. Tetraploid tumours recurred earlier than diploid tumours. None of 6 aneuploid tumours have recurred, although only 3 have been followed beyond 5 years. Multivariate analysis showed that after accounting for grade, none of the other variables, including ploidy, contributed any additional significant prognostic information. Although the results must be regarded as preliminary, in view of the small number of patients with recurrence, they suggest that DNA content offers limited prognostic information in clinically localised prostate cancer.
Sixty consecutive patients were staged clinically by digital rectal examination, acid phosphatase and bone scan prior to radical retropubic prostatectomy and pelvic lymphadenectomy. Twenty-one patients also had magnetic resonance imaging (MRI) and computerized tomography (CT) of the pelvic. The surgical specimens were step-sectioned for pathologic staging. Understaging was documented in 0% of A2 patients, 27% of B1 patients and 67% of B2 patients. Capsular invasion was found in 12% of B1 and 52% of B2 patients, while seminal vesicle extension was documented in 18% of B1 and 52% of B2 patients. Lymph node metastases occurred in 3% of B1 and 29% of B2 patients. Clinical staging error was related to tumor size, tumor grade and history of prior TURP or radiotherapy. Neither CT scan nor MRI improved the accuracy of the digital rectal examination.
The incidence and significance of seminal vesicle invasion in patients with adenocarcinoma of the prostate were determined in 139 patients who underwent radical prostatectomy. Of the 36 patients who had seminal vesicle invasion, 27 (75%) also had capsular invasion and 13 (43%) had lymph node metastases. Disease progression rates were 31% and 58% at 5 and 8 years, respectively. Survival rate at 5 years was 90.6% and at 8 years it was 83.7%. Of the 103 patients without seminal vesicle invasion, 21 (20.4%) also had capsular invasion and 11 (12%) had lymph node metastases. Disease progression rates were 2.5% and 15.7% at 5 and 8 years, respectively. Survival rate at both 5 and 8 years was 98.4%. These data suggest that the majority of patients with seminal invasion do not have lymph node metastases on presentation and thus they cannot be detected by lymph node dissection before radical prostatectomy. Improved techniques for preoperative detection of seminal vesicle invasion can assist in patient selection for surgery and improve the results of radical prostatectomy.
Chronic primary infections with Heligmosomoides polygyrus (Nematospiroides dubius) are still relatively poorly documented, particularly in relation to the role of host resistance in limiting worm survival. In the present work the duration of infection with H. polygyrus was studied in CFLP mice given doses of infective larvae ranging from 50 to 500 L3. The least heavily infected (50 L3) group ceased egg production earliest (week 36) whereas eggs were still detected in the faeces of mice given 500 larvae in week 42. At autopsy (week 42) mice given 50 larvae had virtually lost their entire worm burden with 5 out of 11 mice still harbouring a single worm each. However, all the mice in the group given 500 larvae were still infected, the highest worm burden being 93. The concentration of serum IgG1 and specific antibody was highest in mice given 500 larvae, but sera taken from mice with declining worm burdens 19-38 weeks post-infection did not contain detectable host-protective antibody. During the course of infection in CFLP mice, H. polygyrus sustained irreversible changes in its capacity for subsequent survival. Thus, adult worms transferred to naive mice 2, 7, 14, 30 or 36 weeks post-infection did not live longer than worms of a comparable age in the respective donor group. In contrast, primary infection worms taken from jirds in which expulsion is usually completed by 6 weeks post-infection, re-established in mice and survived considerably longer than in the group of donor jirds. These results were discussed in relation to the possible interactions between parasite senility and immunomodulation, and host resistance in limiting primary infections with H. polygyrus in mice and jirds.
The effect of essential fatty acid (EFA) deficiency on the activities of several membrane-bound enzymes was examined in the brains of C57BL/6J mice. Pregnant females were placed on an EFA-deficient diet during the last week of gestation and their progeny were examined at intervals up to 16 weeks after birth. Early signs of the deficiency, such as reduced body and brain weight, were noted in the mice on the experimental diet. The fatty acid ratio of 20:3w9/20:4w6, a biochemical index of EFA deficiency, rose progressively in the deficient brains from 0.17 at 4 weeks to 0.68 at 16 weeks. Only one of the membrane-bound enzymes studied, i.e. ATPase, demonstrated any consistent significant alteration in specific activity as a consequence of the deficiency. The accumulation of myelin, as measured by the levels of myelin basic protein, was reduced from the earliest age studied. These findings suggest that EFA deficiency does not exert a general, nonspecific effect on all membranes in the brain and that hypomyelination is a major effect of EFA deficiency on brain development.
Cytomegalovirus (CMV) pneumonitis is a common complication of AIDS. With the development of potentially effective drug therapy, the indications for treatment and best means of diagnosis have become issues of practical importance. We reviewed the clinical records and autopsy material from 54 patients dying with AIDS, 39 (72 percent) of whom had CMV infection documented postmortem by culture and the presence of inclusion bodies. Of the patients with CMV infection, disseminated disease was documented in 23 (59 percent) and pneumonitis in 31 (80 percent). Although the majority of patients with CMV pneumonitis had additional forms of pulmonary pathology, CMV was the only causative agent identified in two patients with severe pulmonary disease. Since CMV can cause severe lung damage and disseminated infection in patients with AIDS, specific treatment may be beneficial. Improved diagnostic technology is needed in this area.
In 21 patients adenocarcinoma of the prostate was staged preoperatively by digital rectal examination, computerized tomography and magnetic resonance imaging. Clinical staging was compared to the postoperative pathological staging. In 11 patients computerized tomography, magnetic resonance imaging and digital rectal examination findings were concordant with the histological examination showing tumors confined to the prostate. In 10 patients no correlation between preoperative staging and histology was noted. Of these cases 8 were understaged by computerized tomography, magnetic resonance imaging and digital rectal examination. In 1 patient magnetic resonance imaging showed false positive findings and in another staging with computerized tomography and magnetic resonance imaging was more accurate than digital rectal examination. Our experience indicates that computerized tomography and magnetic resonance imaging have limited value in the preoperative staging of prostatic carcinoma. Moreover, staging with computerized tomography and magnetic resonance imaging does not significantly improve the information gained by digital rectal examination.
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The antibiotic efrotomycin (I), C59H88N2O20, was isolated from cultures of Nocardia lactamdurans as an amorphous yellow powder. Mass spectral and NMR analyses show that the compound is a glycoside of the known antibiotic aurodox (II), C44H62N2O12. Ozonolysis and hydrolysis of I produced the disaccharide V, 6-deoxy-4-O-(6-deoxy-2,4-di-O-methyl-alpha -L-mannopyranosyl)-3-O-methyl-beta-D-allopyranose. This disaccharide is attached to the 4-hydroxyl group of the hexahydropyran substructure of aurodox via a beta-linkage to C-1 of the allose.