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Biomedical subjects

P Jenkins

Publications and source records attributed to P Jenkins.

At least 19 recordsLinked to original sources
PubMed1992

Modification of accessory activity of sheep monocytes in vitro by a coenurus antigen from Taenia multiceps.

A factor in Taenia multiceps coenurus fluid (TMCF) has previously been shown to modify the accessory activity of murine macrophages in vivo and in vitro. The factor (TMCF-F24) has been purified by ion exchange in a fast protein liquid chromatography (FPLC) system. This study was conducted to determine whether TMCF-F24 is an antigen in naturally occurring cerebral coenuriasis, and whether it can also modify normal sheep blood monocytes. Specific IgG antibodies to TMCF-F24 were detected, using ELISA, in serum and cerebrospinal fluid of sheep with clinical coenuriasis. Alterations in monocyte accessory activity were detected by an assay which measured the rate of increase in mitogen-induced lymphocyte transformation caused by addition of increasing numbers of the monocytes. Normal monocytes caused a positive increase in lymphocyte transformation. Monocytes incubated with TMCF-F24 caused progressive inhibition of transformation. This factor may therefore modify monocyte-T cell interaction in natural infection.

Animals↗
PubMed1992

The dangers of dairy farming: the injury experience of 600 workers followed for two years.

In order to better understand the work-related injuries sustained on central New York dairy farms, we undertook a two-year population-based study of 600 farmers and farm workers on 201 dairy farms. During the observation period, 1984-1986, 151 persons had 200 injuries, giving an injury rate of 16.6%/year (166 injuries/1,000 workers/year). Men were injured more often than women (p less than or equal to 0.01). Injured workers were older (p less than or equal to 0.01), worked more hours (p less than or equal to 0.001), and had heavier workloads than noninjured workers (p less than or equal to 0.001). The growing and harvest seasons had the most injuries; winter the fewest. More than 2/3 of the injuries occurred in the afternoon. Owners/operators, often the most experienced, knowledgeable people on the farms, were most often hurt. Those working more than 60 hours/week, with greater than 30 acres under tillage/worker, had a relative risk of 2.76 compared with all other workers. The attributable risk for this group was 51%. There were two fatalities, both involved owner/operators. Our findings suggest that previous studies may have underestimated the risks faced by farmers. Dairy farming in central New York is very dangerous work. Those who own and operate these dairy farms are most often hurt and killed. Analysis of events on individual farms will be reported separately.

Accidents, Occupational↗
PubMed1992

The effects of tumour necrosis factor on host-parasite relations in murine Mesocestoides corti (Cestoda) infection.

The regulatory role of tumour necrosis factor (TNF) was investigated in murine infection with tetrathyridia of Mesocestoides corti. Recombinant TNF alpha reduced macrophage larvicidal activity in vitro. M. corti primed mice for TNF release in response to bacterial lipopolysaccharide (LPS) in vivo. TNF activity was amplified 100-fold at 14 days post-infection (p.i.), with a further rise at day 28 p.i. Maximal inflammatory reaction was observed histologically in the liver at the height of TNF activity. Hepatic necrosis was located within inflammatory foci, but not within the vicinity of the parasite itself, suggesting that TNF may contribute to the pathogenesis of infection. Peritoneal cells from infected mice, when stimulated with tetrathyridia in vitro, showed a 4-fold increase in TNF alpha activity at day 14 p.i. However, when peritoneal cells were stimulated with LPS in vitro, a marked increase in TNF alpha secretion was observed at 2 months post-infection followed by a slow decline. It is suggested that impaired macrophage effector function, previously attributed to endogenous endotoxin, which gains access to peritoneal macrophages through an inability of the liver to detoxify endotoxin, may be mediated through TNF alpha.

Animals↗
PubMed1992

Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin.

OBJECTIVE: To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. DESIGN: A retrospective case notes review. SETTING: The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. PATIENTS: All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. INTERVENTIONS: Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. OUTCOME MEASURES: Response, toxicity and survival. RESULTS: Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. CONCLUSIONS: Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.

Acquired Immunodeficiency Syndrome↗
PubMed1992

[Evaluation of a peptide preparation (milk) in the care of infants with various gastrointestinal intolerances].

The use of an enteral peptide feed based on hydrolysed whey protein (Pepti Junior, Cow and Gate/Nutricia Ltd.) was evaluated in 17 patients with complex GIT intolerance. Nine post surgical neonates were weaned onto the feed either following a period of parenteral nutrition (8) or after demonstrating intolerance of both breast milk and a lactose-free soy based formula. Eight infants admitted to a gastroenterology ward with multiple protein intolerances were also studied. Patients were fed to their nutritional requirements with the milk containing/100 ml; 67 kcal (280 kJ), 2.0 g protein, 3.7 g fat (50% MCT, 50% vegetable oil) and 6.7 g carbohydrate (98% maltodextrins). Patients were maintained on the feed for 7-45 weeks (mean 21 weeks). Full nutritional support was possible with the new formula in all but 2 children who had jejunostomies; in these patients > 50% of nutritional requirement were supplied by the enteral feed. All patients gained weight (mean 0.16 kg/week) (SD 0.09). With the exception of subclinical selenium deficiency, no abnormalities of haematological, biochemical or vitamin states were observed. Post prandial plasma amino-acid concentrations were within acceptable limits and similar to those reported on standard whey based infant formulae. The feed appeared well tolerated in infants with GIT intolerances with no major complications in long term usage.

Evaluation Studies as Topic↗
PubMed1991

Modification of cellular immunity by Taenia multiceps (Cestoda): accessory macrophages and CD4+ lymphocytes are affected by two different coenurus factors.

Taenia multiceps coenurus fluid was analysed by fast protein liquid chromatography in order to separate the factors responsible for previously reported modification of immunological activity in macrophages and T-cells. One factor, F7, was found to be mitogenic for murine L3T4+ T-cells, to be macrophage dependent, to require macrophage compatibility at the I region of the H2 complex, to increase the sensitivity of T-cells to regulatory signals from macrophages and to increase the rate of generation of splenic rosette-forming cells (RFC) against sheep red cells. A second factor, F24, was found to alter macrophages so as to render them suppressive, rather than stimulatory, for parasite-activated and Con A-activated lymphocyte transformation, to depress the rate of generation of RFC and to antagonize the mitogenic effect of F7. The combined actions of these two factors are, therefore, sufficient to explain the known immunomodulatory effects of the metacestode.

Animals↗
PubMed1991

Differential regulation of murine Mesocestoides corti infection by bacterial lipopolysaccharide and interferon-gamma.

Many liver-invasive parasites cause extensive liver damage which may result in an impaired ability to catabolize endotoxin. The influence of endogenous endotoxin on the progress of liver-invasive parasitic diseases has been investigated in murine Mesocestoides corti infection. Invasion of liver tissue by tetrathyridia resulted in extensive parenchymal destruction with fibrosis. In association with this, undetoxified endotoxin, in potentially biologically active concentration, was found on peritoneal macrophages, 5 months post-M, corti infection. Host susceptibility was influenced by the Lps gene for responsiveness to lipopolysaccharide (LPS). The parasite burden of LPS-responsive (C3H/HeN) mice was significantly increased in the livers of these mice when compared to LPS-resistant (C3H/HeJ) mice. LPS reduced the ability of normal peritoneal macrophages to kill tetrathyridia, when co-cultured in vitro. LPS also abrogated the ability of recombinant interferon-gamma (r.IFN-gamma) to enhance macrophage larvicidal activity. These in vitro findings were confirmed in vivo. Daily intraperitoneal administration of LPS, at low concentration, caused a 4-fold increase in parasite burden in the liver, while r.IFN-gamma at optimal concentration reduced parasite burden by 57%. Post-infection macrophages have previously been shown to be refractory to cytokine-activation for larval killing. In this report, we conclude that (1) this refractoriness may be due to the presence of undetoxified endotoxin on post-infection macrophages and (2) endotoxin may reduce host resistance by abrogating effector macrophage response to IFN-gamma.

Animals↗
PubMed1991

Lymphoreticular responses to metacestodes: Taenia multiceps (Cestoda) can modify interaction between accessory cells and responder cells during lymphocyte activation.

This study was designed to test the accessory function of macrophages after activation with products of Taenia multiceps coenuri. Activation was carried out by intraperitoneal injection of mice with coenurus fluid or protoscolex culture supernatant, and function was assessed by adding these macrophages in progressively increasing numbers to macrophage-depleted lymphocyte cultures transforming under the influence of plant mitogens or coenurus-fluid mitogen. In contrast to normal macrophages, which have a progressively enhancing action on the above reactions, parasite-activated macrophages at similar concentrations were progressively inhibitory. However, low concentrations of the activated macrophages enhanced mitosis as well as, or better than, normal. Lymph node cells from injected mice showed abnormal response to macrophage-derived signals. In particular there was subnormal reaction to macrophages in the presence of coenurus mitogen. These results suggest that T. multiceps coenuri may survive in the host because of their ability to reduce effective interaction between lymphocytes and accessory cells.

Animals↗
PubMed1991

Echinococcus multilocularis antigens modify accessory cell function of macrophages.

Peritoneal macrophages and splenic lymphocytes were collected from BALB/c mice, normal or previously infected with Echinococcus multilocularis. In an accessory cell function assay, peritoneal macrophages, in increasing numbers, were added to cultures of splenic lymphocytes. Cultures were stimulated by concanavalin A (Con A) or E. multilocularis culture supernatant (EMSN). Post-infection macrophages, unlike normal macrophages, suppressed Con A- and EMSN-driven lymphocyte transformation. Modification of accessory cells could also be repeatedly induced in vivo by EMSN or a single FPLC fraction of EMSN. Lymphocytes were made more sensitive to accessory cell signals following incubation with EMSN.

Animals↗
PubMed1991

The effectiveness of labetalol compared to hydrochlorothiazide in hypertensive black patients.

Labetalol and hydrochlorothiazide (HCTZ) were compared for their efficacy in controlling hypertension of blacks in a prospective, double-blind study. Sixty-one adult patients with mild to moderate hypertension (standing diastolic blood pressure greater than or equal to 95 mm Hg and less than or equal to 114 mm Hg) were randomly selected to receive either labetalol 100 mg twice daily (n = 30) or HCTZ 25 mg twice daily (n = 31). The study was divided into two phases: a 4-week placebo run-in phase, during which all previous antihypertensive medication was discontinued, and a 12-week drug treatment phase. Labetalol and HCTZ doses were titrated to 400 mg twice and 50 mg twice daily, respectively, during the first 6 weeks of the drug treatment phase for those patients not achieving blood pressure control (standing diastolic blood pressure less than 90 mm Hg and a decrease of 10 mm Hg from baseline) on initial dosages. By the end of the 12 weeks of drug administration, patients on labetalol experienced a mean decrease of 10 mm Hg in standing diastolic blood pressure compared to a mean decrease of 10.1 mm Hg in patients on HCTZ. No differences were observed between the two treatment groups in reductions of either standing blood pressure or heart rate. While 19 of 30 patients on labetalol (63%) achieved blood pressure control at some point during the study with a mean daily dose of 568 mg, 18 of 31 (58%) HCTZ-treated patients achieved control with a mean daily dose of 72 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗
PubMed1990

Cellular cadmium responses in subpopulations T20 and T27 of human lung carcinoma A549 cells.

Subpopulations T20 and T27, cloned from the human lung carcinoma line A549, differ significantly in their Cd2+ cytotoxic response. T27 has an LC50 of 31 microM Cd2+ and a cytotoxic response threshold of 5 microM Cd2+, whereas the T20s LC50 is 15 microM Cd2+ and there is no observed threshold for cytotoxicity. Cadmium-induced metallothionein (MT) synthesis, cadmium accumulation, glutathione (GSH) content, and Cd2(+)-induced changes in GSH content were studied in T20 and T27 in an attempt to determine the mechanism(s) causing differential cytotoxic response. MT synthesis measured by following Cd2(+)-induced [35S] incorporation into MT was found not to differ between T20 and T27. There is, however, a difference in Cd2+ accumulation between the two subclones. T20 and T27 cells were exposed to 5 microM Cd2+ for different times or to different concentrations of Cd2+ for 8 h. The T27 subline, which is the more Cd2+ resistant, was found to accumulate significantly more Cd2(+)-both as a function of time exposed to Cd2+ and as a function of Cd2+ concentration. The two subpopulations were found to have comparable initial GSH contents, but showed different Cd2(+)-induced changes in [GSH] when the cells were exposed to 5 microM Cd2+. T27 cells maintained their GSH content following Cd2+ exposure but T20 cells showed a Cd2(+)-induced decrease in GSH content. The results indicate that the difference in Cd2+ cytotoxic response between A549--T20 and A549--T27 cells is not attributable to alterations in MT synthesis nor to a difference in initial GSH content. Relative Cd2+ cytotoxicity also does not in these cells correlate with relative Cd2+ accumulation. The fact that T27 cells accumulate more Cd2+ and yet are more Cd2+ resistant than T20 cells suggests that T27 cells have a much more effective non-MT mechanism to handle intracellular Cd2+. This may involve different GSH metabolism and/or yet undefined molecular factors.

Cadmium↗
PubMed1990

Regulation of macrophage-mediated larvicidal activity in Echinococcus granulosus and Mesocestoides corti (Cestoda) infection in mice.

Killing of metacestodes by normal or post-infection macrophages and the regulation of this activity by cytokines were studied in vitro. The protoscolecidal activity of normal macrophages against Echinococcus granulosus was inhibited by a product of naive T-enriched lymphocytes co-cultured with protoscoleces (PSC). By contrast, supernates from co-cultures of Mesocestoides corti tetrathyridia (MCT) and T-enriched or B-enriched normal lymphocytes increased killing of MCT by normal macrophages. Larvicidal activity (against both PSC and MCT) was enhanced by high concentrations of macrophage-activating factors produced by Con A-stimulated rat lymphocytes (Con A-LK), but was reduced by low concentrations of these factors. Activation by synergism between Con A-LK and recombinant interferon-gamma(r. IFN-gamma) was demonstrated in macrophage-mediated killing of MCT at high effector to target ratio. Cytokine-activation of normal or post-MCT infection macrophages was compared. Macrophages from both 8 and 20 week post-infection mice were refractory to lymphokines from lymphocyte-MCT cultures and displayed greatly reduced killing of MCT. Macrophage activation by Con A-LK and r.IFN-gamma was also impaired, implying a general defect in the ability of these post-infection macrophages to respond to macrophage activating signals. The data indicate that two different mechanisms may exist by which metacestodes regulate potentially larvicidal effector mechanisms. E. granulosus can elicit the production of lymphokines suppressive for PSC killing, whereas M. corti appears directly to induce a refractory state in effector macrophages.

Animals↗
PubMed1990

When is it safe to stop patching?

Prior reports indicate that about half of amblyopia patients successfully treated with occlusion subsequently require maintenance patching. This retrospective study was designed to discover what clinical characteristics might be associated with a stable outcome following primary occlusion. Included were 188 patients who: (1) had amblyopia related to strabismus, anisometropia or media opacity; and (2) were followed up for at least one year after successful primary occlusion. Patients who did not comply with treatment or who did not achieve equal vision were excluded. Their ages ranged from 2 to 119 months (mean 29 months). Eighty-eight patients (47%) who required no further occlusion were designated the clinically stable group (CSG). The remaining 100 (53%), who subsequently needed patching because of unequal acuities, constituted the maintenance patching group (MPG). CSG patients were older at the beginning (mean 33 months) and at the end (mean 40 months) of primary occlusion than were MPG patients (means 26 and 31 months). Primary occlusion was more likely to have been discontinued because of equal recognition acuities in CSG patients, while equal fixation behaviour or preferential looking was more likely in MPG patients. Distribution of diagnoses, severity of amblyopia at presentation, and length of follow-up were similar in the two groups. Visual outcomes at last follow-up were slightly better in the CSG (p = 0.002). We conclude that, in general, patching can be safely discontinued after the third birthday. Although follow-up after primary occlusion is important to ensure stable results in all patients, preverbal children are more likely to require maintenance patching.

Age Factors↗
PubMed1989

Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide.

Among 447 hypertensive patients, most with a history of diuretic-induced hypokalemia, 252 developed diuretic-induced hypokalemia while receiving hydrochlorothiazide, 50 mg/d. In a randomized study we evaluated the efficacy of three drug regimens in restoring potassium levels while maintaining blood pressure control: hydrochlorothiazide (50 mg/d) plus potassium supplement (20 mmol/d); hydrochlorothiazide (50 mg/d) plus potassium supplement (40 mmol/d); or hydrochlorothiazide (50 mg/d) with triamterene (75 mg/d) in one combination tablet. In all groups, mean serum levels of potassium rose within 1 week and showed no further change thereafter. However, the hydrochlorothiazide/triamterene and hydrochlorothiazide plus 40 mmol of potassium regimens were significantly more effective in restoring serum potassium levels than was the hydrochlorothiazide plus 20 mmol of potassium regimen. A significant increase in magnesium levels was observed only in the group treated with the hydrochlorothiazide/triamterene combination. Each regimen provided continued control of mild to moderate hypertension.

Adult↗