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Biomedical subjects

J Hannah

Publications and source records attributed to J Hannah.

At least 37 records · Page 2Linked to original sources

The incidence and significance of seminal vesicle invasion in patients with adenocarcinoma of the prostate.

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.

Adenocarcinoma↗

Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): the capacity of adult worms to survive following transplantation to recipient mice.

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.

Animals↗

Effects of essential fatty acid deficiency on mouse brain development.

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.

Animals↗

Cytomegalovirus pneumonitis in patients with AIDS. Findings in an autopsy series.

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.

Acquired Immunodeficiency Syndrome↗

The value of computerized tomography scan and magnetic resonance imaging in staging prostatic carcinoma: comparison with the clinical and histological staging.

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.

Biopsy↗

The structure of efrotomycin.

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.

Anti-Bacterial Agents↗

Nematospiroides dubius in the mouse: evidence that adult worms depress the expression of homologous immunity.

Mice immunized by a single infection with irradiated (25 krad) larvae of N. dubius were very resistant to subsequent challenge. However, when normal larvae were administered together with irradiated larvae at immunization, the acquired immunity expressed against a challenge infection was markedly depressed. It was found that as few as 50 normal N. dubius larvae interfered with the immunity that would have otherwise been elicited by the concurrently administered irradiated larvae, but this depressed response was totally alleviated when the normal worms were removed after completing their development in the intestinal mucosa and before they reached adulthood. Adult N. dubius were transplanted directly into the intestines of mice either 7 days before or after immunization by irradiated larvae; it was shown that the recipient mice were less resistant to challenge than mice which had been sham operated. Transplanted adult worms themselves stimulated very little resistance to challenge in recipient mice. These results established that adult parasites are capable of depressing the expression of homologous immunity in the mouse. The possible mechanisms by which N. dubius might modulate the host's immunological activity at the intestinal level are discussed and it is proposed that this mechanism is of benefit to the parasite in preventing the host from eliminating the worms during a chronic primary function.

Animals↗

Nematospiroides dubius in the jird, Meriones unguiculatus: factors affecting the course of a primary infection.

This project investigated the influence of the age and sex of the host and the level of infection with Nematospiroides dubius on the establishment and duration of a primary infection in the jird. It was found that 30 to 35% fewer worms matured in jirds than in mice and that this proportion was unaffected by the level of infection or by the sex of the host. In contrast the age of the jird was found to be critically important in determining the number of adult worms recovered 14 days after infection. Thus, maximum susceptibility to infection was observed when jirds were 18 to 22 days old. In older jirds susceptibility declined until 30 days after birth and thereafter, when approximately 70% of the infective larvae matured (relative to the number of worms maturing in mice). The duration of a primary infection in jirds was similar in both sexes but was influenced by the level of infection and by the age of the host at infection. Heavier infections (500 larvae) lasted about 10 days longer than low level infections, and expulsion of the parasite occurred even when the host was infected with only five larvae. The duration of a primary infection was markedly prolonged in neonatal jirds, faecal egg counts remaining positive for 54 to 56 days after infection of 12-day-old jirds. These results supply some further baseline data for future work on the biology of N. dubius in the jird and they provide support for the involvement of immunological processes in the termination of primary infections of this parasite in mature jirds.

Aging↗

Quaternary heterocyclylamino beta-lactams: a generic alternative to the classical acylamino side chain.

6 beta-[(1-Substituted-4-pyridinio)amino]penam-3-carboxylates and 7 beta-[(1-substituted-4-pyridinio)amino]ceph-3-em-4-carboxylates have been found to be interesting new classes of antibacterial beta-lactams, readily available by SN2 Ar coupling of fluoro-substituted quaternized pyridines and appropriate amino lactam carboxylic acids. Compared to penicillin G, the penam 12c exhibited a spectrum extended to Gram-negative species, such as Escherichia, Shigella, Klebsiella and Enterobacter, offset by a loss of potency against Gram-positive species. Excluding Pseudomonas, many examples of the cephems showed excellent activity against the above Gram-negative organisms, and in some cases, such as 15i, the spectrum included good performance against the staphylococci and streptococci. With Serratia and many Proteus species, there was an adverse inoculum and medium effect which was not observed in the good Gram-positive reach of the cephem series.

Anti-Bacterial Agents↗

Novel analgesic-antiinflammatory salicylates.

5-(2,4-Difluorophenyl)salicylic acid, diflunisal (25), is the best compound, in terms of both efficacy and safety, from over 500 salicylates investigated in our laboratories. It is a chemically distinct, nonacetylating salicylic acid, more active than aspirin as an analgesic and antiinflammatory agent and superior in duration of action and therapeutic index. Some recent clinical and biochemical observations are briefly discussed.

Animals↗

Synthesis and analgesic-antiinflammatory activity of some 4- and 5-substituted heteroarylsalicylic acids.

We have made a series of 4- and 5-aryl- and 4- and 5-heteroarylsalicylic acid derivatives with the objective of reducing gastric irritation and increasing potency. Here we describe a series of 4- and 5-heterocyclic salicylic acids and their antiinflammatory-analgesic potencies measured in comparison to aspirin. An improvement of the therapeutic index over aspirin of 100 was achieved; however, the heterocyclic salicylic acids lacked antipyretic activity. Some physicochemical parameters which may bear on the antiinflammatory activity of these compounds are discussed.

Animals↗

Substituted pyrazolo corticoids as topical antiinflammatory agents.

The synthesis of a series of substituted pyrazolo corticoids is described. Of these 11beta,17alpha,21-trihydroxy-6,16alpha-dimethyl-4,6-pregnadieno[3,2-c]-2'-(4-pyridly)pyrazole (21) shows an excellent separation of systemic to local activity in the model animal test. Compound 21 exhibits high vasoconstriction activity in human volunteers and is clinically effective in the treatment of psoriasis.

Administration, Topical↗

Noncovalent binding of a spin-labeled inhibitor to ribonuclease.

The stable free radical 2,2,6, 6-tetramethyl-4-hydroxypiperidin-1-oxyl monophosphate has been synthesized; it binds to ribonuclease. The selective changes in the nuclear magnetic resonance spectrum of the enzyme produced by the free radical make it possible to define qualitatively the region of the enzyme to which it binds. The radical appears to occupy a site similar to that to which inorganic phosphate binds which is close to or within the active site of the enzyme.

Binding Sites↗