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Biomedical subjects

D Lambert

Publications and source records attributed to D Lambert.

At least 55 records · Page 3Linked to original sources

Prospective evaluation of protein bound vitamin B12 (cobalamin) malabsorption in the elderly using trout flesh labelled in vivo with 57Co-cobalamin.

BACKGROUND: The frequency of dietary protein bound vitamin B12 malabsorption in elderly patients remains controversial. AIMS: To evaluate this malabsorption in elderly hospitalised patients using a modified Schilling test. PATIENTS: Fourteen elderly patients with low B12 blood levels were prospectively selected from 394 hospitalised patients. METHODS: The modified Schilling test was performed with trout labelled in vivo. RESULTS: The test was normal in five healthy elderly subjects, in 7/8 patients with pancreatic insufficiency, and in nine non-elderly patients with antral gastritis. The low decision limit was established at 3.3% (median 4.8%). From the 14 elderly patients with low B12 prospectively selected from 394 hospitalised patients, seven had a real deficiency with anaemia and an increased homocysteine and/or methylmalonate serum level. The modified Schilling test showed malabsorption in five of these patients, including two in which the standard Schilling test was normal, and three in which the standard Schilling test was partially corrected by an intrinsic factor. CONCLUSIONS: Protein bound vitamin B12 malabsorption was detected in at least 0.5% of elderly hospitalised patients, using the labelled trout flesh absorption test.

Adult↗

Alcoholic cirrhosis and cobalamin metabolism.

The cobalamin status of 27 patients suffering from alcoholic cirrhosis and 20 control subjects was analyzed. Plasma cobalamin (p < 0.005), total corrinoids (p < 0.005) and their analogs (p < 0.05) were all significantly elevated in the cirrhosis patients. These differences were due to increased haptocorrin (HC)-bound corrinoid (p < 0.02), which could be explained by a deficient hepatic clearance of cobalamin bound to HC. The increase in the concentration of true cobalamin was greater than that of its analogs. There were positive correlations between cholestasis (serum alkaline phosphatase) and plasma analog concentrations (p < 0.05), HC-bound cobalamin (p < 0.005) and total corrinoids bound to HC (p < 0.005). The plasma concentrations of the indicators of cobalamin deficiency, homocysteine (p < 0.05) and methylmalonic acid (p < 0.001), were increased, which could indicate poor cellular penetration of vitamin B12 or a defect in the activation of the two vitamin-B12-dependent enzymes.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

A randomized comparison of the clinical and hormonal effects of two GnRH agonists in patients with prostate cancer.

OBJECTIVE: The aims of the study were (i) to compared the efficacy of the two long-acting GnRH agonists (GnRHa) triptorelin (Trp) and leuprolide (Leu) in men with prostate cancer and (ii) to assess the pattern of plasma testosterone levels following each injection of GnRHa. PATIENTS AND METHODS: 67 patients referred for prostate cancer not suitable for surgery were randomly allocated to two treatment regimens: 33 patients received 3.75 mg Trp i.m. at 4-week intervals for 3 months and 34 patients were treated with 3.75 mg Leu s.c. at the same rhythm of administration for 3 months. RESULTS: Clinical data at entry and assessed monthly during follow-up did not differ between the two groups. Plasma prostate-specific antigen (PSA) and testosterone were measured before, 24 and 72 h after each injection of GnRHa. During treatment, PSA dropped similarly in both groups. By month 2, testosterone was < 1.0 nmol/l in 77 and 48% of patients treated with Trp and Leu, respectively (p = 0.02). 24 and 72 h after GnRHa injection, 77 (Trp) and 56% (Leu) of patients had testosterone < 1.0 nmol/l (p < 0.05). CONCLUSIONS: The second and third injections of GnRHa were not followed by a significant increase in testosterone. Trp induced a higher decrease in testosterone than did Leu. The implications in terms of survival should, however, be studied in a larger and longer study.

Antineoplastic Agents, Hormonal↗

[Lyme borreliosis].

Lyme disease is the most common of tickborne spirochetoses in France. Over fifty years, several clinical forms have been identified. Following the description of the disease in the United States, links were recognised between the forms presenting infectious, cutaneous, neurological and rheumatic symptoms. Although its epidemiology has now been well established, this spirochetosis can still pose difficult diagnostic problems despite serological investigations. Concerning therapy, rapid treatment is highly valuable. The prescription of ceftriaxone is now highly recommended.

Humans↗

Effect of glucose deprivation on rat glutamine synthetase in cultured astrocytes.

Glutamine synthetase was purified from the cerebral cortex of adult rats and characterized. Polyclonal rabbit antibodies were raised against the enzyme, purified and their specific anti-(glutamine synthetase) activity determined. A primary astroglial culture was prepared from newborn Sprague-Dawley rats. Astrocytes at different ages of development were incubated in the presence and absence of glucose. In glucose-deprived conditions the specific activity of glutamine synthetase decreased. This decrease was more pronounced in 8-day-old than in 21-day-old cultures. Kinetic analysis demonstrated that the reduction in activity was mainly related to a decrease in Vmax. By immunoprecipitation, it was shown that the number of enzyme molecules in astrocytes was decreased in glucose-deprived conditions. On addition of glucose, a total recovery of glutamine synthetase was obtained after 36 h in 8-day-old culture. Rates of degradation and synthesis were investigated. When compared with an incubation in the presence of glucose, glucose deprivation increased enzyme turnover, as estimated from the first-order disappearance of radioactivity from glutamine synthetase. Synthesis rate was estimated from the incorporation of [35S]methionine during a 2 h incubation period and was decreased in glucose-deprived conditions. Trichloroacetate-precipitable proteins changed only slightly in the experimental conditions, and total protein did not vary significantly during the experimental period. A mathematical model is presented which attempts to integrate degradation and synthesis in our experimental model.

Age Factors↗

Crohn's disease and vitamin B12 metabolism.

The concentrations of vitamin B12, its analogs, and the haptocorrin and transcobalamin carriers in 21 patients suffering from Crohn's disease and a group of controls (20 adults) were measured. There were no significant differences in the mean values for vitamin B12, total corrinoids (vitamin B12 + analogs), or vitamin B12 or total corrinoids bound to haptocorrin or transcobalamin of the Crohn's and control patients. There was a significant increase in the binding capacity of transcobalamin in the Crohn's patients compared to the controls (P < 0.001), but there was no difference in the binding capacities of haptocorrin. The serum concentrations of the markers of vitamin B12 status, homocysteine and methylmalonic acid, showed an increase (P < 0.01) in homocysteine in the Crohn's disease patients, but no change in methylmalonic acid. As the hyperhomocysteinemia was associated with normal folate concentrations, there may have been a defect in the activation of the enzyme due to altered intracellular vitamin B12 status.

Adult↗

Effects of SKF 108922, an HIV-1 protease inhibitor, on retrovirus replication in mice.

Rationally designed synthetic inhibitors of retroviral proteases inhibit the processing of viral polypeptides in cultures of human T lymphocytes infected with human immunodeficiency virus type 1 (HIV-1) and therefore suppress the infectivity of HIV-1 in vitro. We have previously reported the antiviral activity in vitro of HIV-1 protease inhibitors against the C-type retrovirus Rauscher murine leukemia virus (RMuLV) and the lentivirus simian immunodeficiency virus (SIV). The same compounds which blocked the infectivity of HIV-1 also inhibited the infectivity of RMuLV and SIV in vitro. This report extends these findings by testing the antiviral activity of HIV-1 protease inhibitors in vivo in the RMuLV model. RMuLV-infected mice were treated twice a day (bid) with either an active (SKF 108922) or inactive (SKF 109273) compound for fourteen days by the intraperitoneal (i.p.) route. Compared with excipient control, SKF 108922, formulated with hydroxypropyl-beta-cyclodextrin (HPB), reduced virus-induced splenomegaly, viremia, and serum reverse transcriptase (RT) levels, while SKF 109273 was inactive. The HPB vehicle by itself enhanced replication of RMuLV. The effects of changing the formulation and the route of administration were examined. SKF 108922, formulated in HPB, had similar antiviral activity when administered by the i.p. or subcutaneous (SC) routes. However, SKF 108922 administered as a colloidal suspension in cholesterol sulfate (CS) had no detectable antiviral effect. Measurements of the circulating levels of the protease inhibitor in plasma explained this result. Plasma concentrations of SKF 108922 exceeded 1000 nM within 10 min after SC administration of the compound solubilized in HPB, but SKF 108922 was not detected in plasma after SC administration of the same dose formulated with CS. Information on optimal conditions for administering these agents should prove useful in guiding their clinical application Therefore, RMuLV should provide a good model for the preclinical evaluation and development of this class of agents for the treatment of HIV.

2-Hydroxypropyl-beta-cyclodextrin↗

Increased incidence of cancer in first degree relatives of women with double primary carcinomas of the breast and colon.

Breast and colon cancer are among the most common cancers in the developed world. Several epidemiological studies suggest that the occurrence of one of these two cancers in a woman may predispose to the development of the other. The occurrence of both forms of cancer in the same woman may be because of chance or common susceptibility. In order to determine how frequently double primary cancers have a hereditary basis, we conducted a registry based study at a single Montreal hospital. Cancer rates in first degree relatives of patients with multiple primaries were compared with provincial age standardised incidence rates and relative risks (RRs) were estimated. In first degree relatives under 45 there was a total of 15 cancers observed, compared with 3.70 expected, giving an RR of 4.05 (95% CI: 2.27-6.68). The RR for colon cancer was significantly increased among male relatives. For relatives less than 45 years old at diagnosis, the RR for colon cancer was 66.7 (95% CI: 13.8-195) (three cases observed, 0.045 expected). For all ages the RR was 5.02 (95% CI: 2.04-10.5). The RR for breast cancer was 5.92 (95% CI: 1.91-13.8) for female relatives under 45 (five cases observed, 0.845 expected) and 2.14 (95% CI: 1.07-3.83) for breast cancer at any age. These results suggest that there may be genes that predispose to both breast and colon cancer in certain people.

Breast Neoplasms↗

Dietary calcium salts as protective agents and laminin P1 as a biochemical marker in chemically induced colon carcinogenesis in rats.

To evaluate the protective effect of different calcium forms against colon carcinogenesis, Wistar rats fed a high-fat diet (24%) were supplemented with different chemical forms of dietary calcium and were intrarectally instilled with N-methyl-N-nitrosourea (NMU). Supplemental calcium was administered at 1.5% mineral (w/w of total diet) complexed with either carbonate, gluconate, or lactate in Groups 2, 3, and 4, respectively. The tumor incidence of colon cancer was compared with a control group (Group 1), fed the same diet without supplemental calcium. Colon carcinoma incidence was 31, 33, 13, and 7% in Groups 1, 2, 3, and 4, respectively. Calcium had a significant protective effect against carcinogenesis, and the maximum protective effect was observed with gluconate and lactate forms. Laminin P1 blood level was measured as a tumor marker. Laminin P1 results were compared with the reference group (Group T), fed a standard diet and not NMU instilled. The serum laminin P1 level was significantly higher (p = 0.0001) in NMU-instilled Groups 1, 2, 3, and 4 (0.24 +/- 0.03, 0.93 +/- 1.43, 0.84 +/- 1.33, and 0.41 +/- 0.34 mU/ml respectively) than in the Reference Group T (0.10 +/- 0.05 mU/ml).

Animals↗

Prospective audit of abdominal aortic aneurysm surgery in the northern region from 1988 to 1992. Northern Vascular Surgeons Group.

Over a 5-year period a prospective audit was carried out on 1131 patients undergoing surgery for abdominal aortic aneurysm (AAA) in the northern region. A total of 470 operations was performed in teaching hospitals and 661 in district hospitals; emergency operations accounted for 41.5 per cent. The overall mortality rate was 25.8 per cent; for emergency cases this value was 50.0 per cent. Mortality rates for elective surgery were 3.9 per cent in teaching and 12.0 per cent in district hospitals. Patients with ruptured AAA admitted via the accident and emergency department had a higher mortality rate (64.3 per cent) than those admitted by their general practitioner (49.5 per cent) or those referred from the urology department (18.8 per cent). In all, 73 (6.5 per cent) patients were admitted with an alternative diagnosis, ranging from collapse of unknown cause (25) to torsion of the testes (one) and colonic obstruction (one). Age had a profound effect on mortality rates. For emergency cases the mortality rate varied from 47.0 per cent (in teaching plus district hospitals) in those aged less than 80 years to 70.1 per cent in those 80 years or over (chi 2 = 7.22; P = 0.007). For elective surgery the mortality rate varied from 7.6 per cent (in teaching plus district hospitals) in those under 80 years to 23.8 per cent in those 80 years or over (P = 0.0006). The overall mortality rate of 25.8 per cent is significantly less than that quoted in the Confidential Enquiry into Perioperative Deaths report of 1987. Furthermore, elective patients over 80 years of age may expect a survival rate of 76 per cent and, in the absence of major medical contraindications, should not automatically be denied surgery. Importantly, it is of note that this prospective audit identified 31 per cent more cases than recognized by regional audit data.

Aged↗

Analysis of ecdysteroid action in Malacosoma disstria cells: cloning selected regions of E75- and MHR3-like genes.

IPRI-MD-66 (MD-66) cells respond to 20-hydroxyecdysone (20E, 4 x 10(-6) M) in the medium by producing cytoplasmic extensions, clumping and attaching themselves to the substrate. These morphological changes are at a maximum by 6 days post treatment. Degenerate oligonucleotides, designed on the basis of conserved amino acid sequences in the DNA and ligand binding regions of the members of the steroid hormone receptor superfamily, were used in RNA-PCR to isolate two cDNA fragments, Malacosoma disstria hormone receptor 2 (MdHR2) and Malacosoma disstria hormone receptor 3 (MdHR3) from the MD-66 cells. Comparison of deduced amino acid sequences of these cDNA fragments with the members of the steroid hormone receptor superfamily showed that MdHR2 is most closely related to E75 proteins of Manduca sexta, Galleria mellonella and Drosophila melanogaster. The MdHR3 is most closely related to Manduca hormone receptor 3 (MHR3), Galleria hormone receptor 3 (GHR3) and Drosophila hormone receptor 3 (DHR3) proteins. At a concentration of 4 x 10(-6) M, 20E induces the expression of MdHR2 and MdHR3 beginning at 3 h, reaching maximum levels in 12 h and declining in 24 h. MdHR2 binds to a 2.5 kb mRNA, whereas MdHR3 binds to a 4.5 kb mRNA. Based on sequence similarity, RNA size and ecdysone inducibility, we conclude that these cDNA fragments, cloned from MD-66 cells, are regions of E75- (MdHR2) and MHR3- (MdHR3) like genes.

Amino Acid Sequence↗

Freehand technique to harvest partial-thickness skin to repair superficial facial defects.

BACKGROUND: The freehand-scalpel technique to harvest skin for grafting is a forgotten surgical art. Modern facial surgeons prefer to use local skin flaps or Wolfe-type full grafts to repair facial defects. OBJECTIVE: To determine the relative merits and cosmetic results of freehand skin grafts to cover facial defects following Mohs surgery. METHODS: We used the freehand-scalpel technique to harvest skin from the periauricular region of the neck and cheek, and other sites. After a local anesthetic is injected the number 15 or 10 blade is used to harvest skin by sequential tangential incisions. The average dermal thickness was about 1.0 mm. To improve cosmetic appearance, the overall shape and thickness of the graft was contoured during harvesting to fit cosmetic unit or facial line. RESULTS: For more than 5 years we have used the freehand technique to repair superficial facial defects of the nose, ear, scalp, temple, forehead, and other nonhead sites. A total of 65 freehand procedures were performed to repair facial defects. The distribution of the anatomic sites and sizes are presented. The size ranged from less than 1 cm to greater than 5 cm in diameter. Three typical cases are presented to illustrate the gratifying results that can be obtained with this technique. CONCLUSIONS: In selected sites and patients, the freehand graft is a rapid and convenient method of harvesting skin. When harvested from the preauricular cheek and subauricular neck, the graft is a good match to cover sun-exposed defects of the nose and ear. The major advantages of the freehand technique are that: 1) it expands the number of potential donor sites from which to select the most compatible skin to cover facial defects; 2) it allows the surgeon to efficiently configure the graft to the desired shape and depth to conform to the cosmetic unit or defect that is being reconstructed; 3) it does not require a dermatome or other specialized instrument to perform; and 4) it achieves wound repair with good appearance and function. The freehand partial-thickness skin graft has become our preferred method of grafting superficial facial defects.

Ear↗

Access of rural AFDC Medicaid beneficiaries to mental health services.

This article examines geographic differences in the use of mental health services among Aid to Families with Dependent Children (AFDC)-eligible Medicaid beneficiaries in Maine. Findings indicate that rural AFDC beneficiaries have significantly lower utilization of mental health services than urban beneficiaries. Specialty mental health providers account for the majority of ambulatory visits for both rural and urban beneficiaries. However, rural beneficiaries rely more on primary-care providers than do urban beneficiaries. Differences in use are largely explained by variations in the supply of specialty mental health providers. This finding supports the long-held assumption that lower supply is a barrier to access to mental health services in rural areas.

Aid to Families with Dependent Children↗

[Purulent pericarditis in dermatopolymyositis].

The authors report the case of a 33-year-old patient with dermatopolymyositis, admitted to hospital for acute cystic pericarditis with fever and deterioration of the general state. The aetiological diagnosis was obtained by analysis of the pericardial fluid after surgical drainage, revealing purulent Staphylococcus aureus pericarditis. This case emphasises that, despite the marked rarity of pericardial effusion in the course of dermatopolymyositis, due to the steroid sensitivity of this disease, the possibility of septic contamination should be considered in the presence of persistent pericarditis in the context of this disease.

Adult↗

[Verrucous carcinoma. Nosologic aspects, apropos of 4 cases].

INTRODUCTION: The nosology of verrucous carcinomas is a complicated problem. The name given to each manifestation may vary with localization. We report our findings in four cases with this skin disease. CASE REPORTS: Four patients, 76, 52, 76 and 55 years of age, presented with verrucous carcinoma. In the first case, the disease began with a chronic varicose ulceration localized on the anterolateral aspect of the right leg. In the second, the lesion was localized on the lateral aspect of the right leg facing a zone showing signs of repeated microtraumatisms. HPV-18 was isolated in this patient. The third case had a vegetating lesion on the dorsal aspect of the right hand, simulating a wart. The fourth case is a historic case in which a voluminous tumour developed over several years on an ulceration of the medial aspect of the left malleole, associated with trauma and venous insufficiency. COMMENTS: The three recent cases did not raise any particular problem with diagnosis. The diagnosis in the historical case, published in 1969 as a vegetating pyoderma, was corrected later. This illustrates the nosology problems raised in this particular form of epidermoid carcinoma which often has an impressive clinical presentation and a reassuring histology. The group of verrucous carcinomas include different skin or mucosal lesions formerly designated as oral florid papillomatosis, Buschke-Löwenstein acuminate condyloma or pseudo-epitheliomatous vegetating pyoderma. Cuniculatum epithelioma was added to this group for simplification although this rarely observed lesion is a separate entity. CONCLUSION: The pathology diagnosis of verrucous carcinoma requires large and deep biopsy. Treatment is surgical and regular follow-up is needed as for all malignant tumours.

Aged↗