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At least 19 recordsLinked to original sources
PubMed2000

Technology evaluation: transgenic alpha-1-antitrypsin (AAT), PPL therapeutics.

PPL Therapeutics is developing transgenic alpha-1-antitrypsin for the treatment of cystic fibrosis lung disease and other conditions in which connective tissue is broken down irreversibly. AAT is a plasma protein that inhibits elastase, a key player in the inflammatory response that, unchecked, will lead to excessive tissue destruction. PPL has taken transgenic alpha-1-antitrypsin through phase II clinical trials in the cystic fibrosis lung, delivering it in aerosol form to assess its safety and efficacy [315887]. Although early results are not statistically relevant with respect to clinical benefit, they do show some promise, especially given the low numbers of patients studied and the complex phenotypes and severities associated with cystic fibrosis.

Animals↗
PubMed2002

Control of propranolol intake by direct chromatographic detection of alpha-naphthoxylactic acid in urine.

A rapid chromatographic procedure with a C18 column, a mobile phase of 0.15 M sodium dodecyl sulfate (SDS)-10% (v/v) 1-propanol at pH 3 (0.01 M phosphate buffer), and fluorimetric detection, is reported for the control of propranolol (PPL) intake in urine samples, which are injected directly without any other treatment than filtration. The peak of PPL was only observed in samples taken a few hours after ingestion of the drug due to its extensive conjugation and metabolisation. The detection of several unconjugated PPL metabolites was therefore considered: desisopropylpropranolol (DIP), propranolol glycol (PPG), alpha-naphthoxylactic acid (NLT) and alpha-naphthoxyacetic acid (NAC). NLT showed the best characteristics: it eluted at a much shorter retention time than PPL, its concentration in urine samples was greater and it did not present any interference from endogeneous compounds in urine, common drugs or drugs administered in combination with PPL. The limit of quantification, measured as the concentration of analyte providing a relative standard deviation of 20%, was 24 ng/ml, and the day-to-day imprecision was below 4% for concentrations above 200 ng/ml. The procedure allows the routine control of PPL at therapeutic urine levels. Urinary excretion studies showed that the detection of NLT is possible at least up to 20-30 h after oral administration.

Adrenergic beta-Antagonists↗
PubMed2006

The relationship of pleural pressure to symptom development during therapeutic thoracentesis.

STUDY OBJECTIVE: To describe the relationship of patients' symptoms during therapeutic thoracentesis to pleural pressure (Ppl). DESIGN: Review of prospectively collected data during 169 therapeutic thoracentesis procedures. SETTING: University Hospital in Boston, MA. PATIENTS AND METHODS: One hundred sixty-nine patients who had Ppl measured during therapeutic thoracentesis were included in this study. End-expiratory pressures were measured after the withdrawal of 5 mL of fluid and every 240 mL thereafter until the pressure was lower than -20 cm H(2)O, chest discomfort developed in the patient, or no more fluid could be removed. Patients' symptoms, including chest pain, chest discomfort, and cough were recorded simultaneously. RESULTS: There was no correlation between the amount of pleural fluid removed and the development of symptoms. The closing pressures and the total change in Ppl (see the "Materials and Methods" section for definitions), however, were significantly lower in the group of patients who experienced chest discomfort compared to patients who developed cough or were asymptomatic. There was also a trend toward a significantly lower pleural elastance in patients who developed cough compared to that in the other two groups. Additionally, only 22% of patients in whom chest discomfort developed, and 8.6% of patients in whom symptoms did not develop, had potentially dangerous Ppl values (ie, lower than -20 cm H(2)O). CONCLUSIONS: The development of chest discomfort is associated with a potentially unsafe drop in Ppl values and should be a sign to terminate thoracentesis. It is not necessary to terminate thoracentesis solely because of the development of cough. Without attention to pleural manometry, a significant percentage of patients may develop potentially dangerous Ppl. Although we recommend pleural manometry with all thoracenteses, when it is not used attention to symptoms remains a valuable surrogate.

Aged↗
PubMed2003

A new activated factor X-based clotting method with improved specificity for procoagulant phospholipid.

An improved activated factor X-based clotting method was used to investigate activity of procoagulant phospholipid (PPL) in blood samples collected into various anticoagulants and in plasmas with a range of abnormalities. The dilute activated factor X-activated clotting time (XACT) was carried out on a mixture of specimen with phospholipid-free porcine plasma. PPL from the test sample is then rate-limiting, controlling the clotting time so that the XACT is shortened from a maximum of approximately 120 s with citrated platelet-free plasma to approximately 30 s with freeze-thawed platelet-rich plasma. XACT results were only shortened slightly by fresh normal platelet-rich plasma, but were shortened significantly by platelets that had been activated by freeze-thawing. This improved method for PPL was not prolonged by deficiencies of known clotting factors and therapeutic levels of heparin, and it was surprisingly resistant to most lupus anticoagulants. However, it was extremely sensitive to PPL, detecting down to 50 ng/ml synthetic phospholipid added to phospholipid-free plasma. Excellent correlation was achieved between XACT shortening and microparticle count assessed by annexin V-binding and flow cytometry in normal plasma spiked with platelet microparticles. In citrated blood specimens, XACT shortened with time in a temperature-dependent manner. XACT results on blood samples anticoagulated with ethylenediamine tetra-acetate were more stable, and these would be preferable for assessing PPL expression ex vivo. XACT was significantly shorter in whole blood samples than in normal platelet-rich or platelet-poor plasmas, suggesting that PPL was normally expressed more by cells or aggregates larger than platelets or microparticles.

Annexins↗
PubMedDate not supplied

Synthesis and screening of a rationally designed combinatorial library of affinity ligands mimicking protein L from Peptostreptococcus magnus.

Rational design and combinatorial chemistry were utilized to search for lead protein L (PpL) mimetics for application as affinity ligands for the purification of antibodies and small fragments, such as Fab and scFv, and as potential diagnostic or therapeutic agents. Inspection of the key structural features of the complex between PpL and human Fab prompted the de novo design and combinatorial synthesis of a 169-membered solid-phase ligand library, which was assessed for binding to human IgG and subsequent selectivity for the Fab fragment. Eight ligands were selected, chemically characterized and compared with a commercial PpL-adsorbent for binding pure immunoglobulin fractions. The most promising lead, ligand 8/7, when immobilized on an agarose support, behaved in a similar fashion to PpL in isolating Fab fragments from papain digests of human IgG to a final purity of 97%.

Affinity Labels↗
PubMed1998

Study on the suitability of a rat model for tardive dyskinesia and the preventive effects of various drugs.

1. Male Sprague-Dawley rats (weighing 260-300 g) were administered 1.5 mg/kg of haloperidol (HPD) intraperitoneally once daily for 28 days to produce an animal model for tardive dyskinesia (TD). The daily administration of HPD significantly increased the frequency of involuntary orofacial movements (chewing movements, tongue protrusions and buccal tremors). 2. Its suitability as a model for TD was assessed in terms of the therapeutic effects of 6 drugs [trihexyphenodyl hydrochloride(THP), clonazepam(CZP), sodium valproate(VPA), alpha-tocopherol(Vit E), ritanserin(RS) and propranolol hydrochloride(PPL)]. These drugs were also used concomitantly with HPD to study their preventive effect. 3. As for the therapeutic effects of the drugs, both the single and the 14-day daily administrations of CZP as well as of VPA significantly suppressed the chewing movements. The results were mostly consistent with the effect of each drug on human TD, indicating this would be an excellent model for TD in terms of the drug responsiveness. 4. The concomitant administration of RS from the start of HPD administration significantly suppressed the appearance of chewing movements. The concomitant administration of Vit E for 42 days also suppressed chewing movements and buccal tremors. On the other hand, the concomitant administration of THP tended to aggravate these involuntary movements. 5. The fact that the therapeutic and preventive effects of the drugs on this model differed suggested that the development and recovery of the movements might also differ, at least in part.

Animals↗
PubMed1989

Effects of pindolol and propranolol on blood lipids in hypertensive patients.

Since beta-blockers could affect lipid levels at the therapeutic dose range in hypertensive patients, a parallel 6-month randomized trial with pindolol (PDL) (16 pts.) and propranolol (PPL) (23 pts.) was designed (mean age = 55 + 7.1 years and 57 + 8.0 years; 9 males, 7 females and 15 males, 8 females, respectively). Total cholesterol, LDL and HDL fractions, and triglycerides (TGs) were determined before (washout phase) and during 1, 3, and 6 months of therapy. Patients were instructed to maintain their usual dietary habits. Daily drug doses were adjusted step by step to attain an optimal hypotensive effect (PDL 15-45 mg, PPL 180-240 mg). In the PPL-treated group, total cholesterol and LDL did not change significantly, HDL decreased (from 45.2 to 40.5 mg/dl, p less than 0.05) and TG increased (from 133 to 169 mg/dl, p less than 0.05). In the PDL group total cholesterol and LDL did not change either, but HDL increased (35.9 to 44.7 mg/dl, p less than 0.01) and TGs, were reduced (from 169 to 131 mg/dl, p less than 0.05). No dose-effect relationship was recorded. It is concluded that pindolol does not negatively influence HDL nor the TG blood lipid profile as does PPL. Accordingly, pindolol might be preferred to propranolol in the treatment of hypertensive patients with an unfavorable lipid profile, but this assumption remains to be proven in larger, prospective, long-term followup trials.

Aged↗
PubMed1991

[Immunoglobulin deficiency after repeated plasmapheresis].

In 10 patients with Guillain-Barré syndrome the level of globulins and immunoglobulins before and after plasmapheresis was investigated. As a plasma substitute either PPL (in 8 patients) or a plasma substitute solution rich in immunoglobulins (in 2 patients) was used. When plasma was substituted with PPL, the globulins and immunoglobulins dropped to a mean of 40% of the initial value (range 30-60%) after the first plasmapheresis. With daily or alternate day plasmapheresis, the globulins only partially recovered. Before the second plasmapheresis they were still reduced to a mean of 50% (range 20-50%), and dropped further with ongoing exchanges to a mean of 33% (range 20-50%) as measured before the third plasmapheresis. Accordingly, there was a loss of immunoglobulins of similar magnitude. With the use of a plasma substitute solution rich in immunoglobulins (IRP), globulins could be maintained at normal levels. The lowest immunoglobulin values measured after plasmapheresis were 6 g/l (normal range 8-17 g/l). One patient developed gram-negative septicaemia after plasmapheresis with PPL, possibly due to a low immunoglobulin concentration. We conclude that a plasma substitute solution rich in immunoglobulins should be used for therapeutic plasmapheresis in order to maintain physiological immunoglobulin concentrations.

Adult↗
PubMed1993

Clinical experience with penicillin skin testing in a large inner-city STD clinic.

OBJECTIVE: To establish (1) the prevalence of positive penicillin skin tests among outpatients with well-defined but variable history of penicillin allergy and (2) the reproducibility, safety, and negative predictive value of skin testing with benzylpenicilloyl polylysine (PPL) and a minor-determinant mixture (MDM). DESIGN: Serial consenting outpatients with current indications for penicillin therapy were skin-tested in duplicate with PPL and MDM. Subjects with negative skin tests (93% of those positive by history and 95% of those negative by history) received therapeutic courses of benzylpenicillin (81%) or ampicillin (19%). Negative predictive value of skin testing was established by 72-hour follow-up for adverse reactions to drug. SETTING/PATIENTS: A total of 5063 consecutive, qualifying outpatients in a Baltimore, Md, sexually transmitted disease (STD) clinic. The study group was young (73% between 20 and 40 years old), 66% male, and 90% black; 25% had history of atopy. Follow-up was 94% complete. RESULTS: Positive skin tests were observed in 7.1% of 776 individuals with previous history of penicillin allergy and in 1.7% of 4287 subjects negative by history (P << .001). Previous history of anaphylaxis or urticaria was associated with significantly higher rates of positive skin tests of 17.3% and 12.4%, respectively (P<<.001). Only 4% with history of exanthem had positive skin tests (P = .03). The coefficient of variation for duplicate skin tests was 11%. Time intervals since last penicillin treatment did not influence the rate of positive skin tests. Adverse reactions to skin tests occurred in 13 (1.2% of patients positive by history; 9.4% of those with positive skin tests). A mild anaphylactic reaction occurred in one individual whose preliminary scratch testing was inadvertently omitted; systemic pruritus or urticaria occurred in 11 subjects; one had a large local reaction. After penicillin administration to individuals with negative skin tests, acute allergic reactions occurred in 0.5% of subjects negative by history compared with 2.9% of subjects positive by history (chi 2 = 33.3; P = .0001). Reactions were generally mild and self-limited; only two cases of mild anaphylactic reaction occurred, both in patients with history of severe IgE-mediated reaction. CONCLUSIONS: Skin testing with both major and minor penicillin determinants is safe using current recommendations, and both reagents are necessary for maximizing the identification of sensitized subjects. Routine penicillin skin testing can facilitate the safe use of penicillin in 90% of individuals with a previous history of penicillin allergy.

Adult↗
PubMed1994

[Prolymphocytic leukemia: the therapeutic strategy].

Prolymphocytic leukemia (PLL) is a malignant lymphoproliferative disorder, characterized by massive splenomegaly, predominance of prolymphocytes in the peripheral blood and bone marrow, minimal lymph nodes enlargement and poor prognosis. It accounts for a 5-10% case of chronic lymphocytic leukemia (CLL). Patients age is usually over the fifth decade, the disease is 4.1 more common in males. More than 80% are B-lymphocytic derived cells showing a post-thymic phenotype. Median survival of B-PLL patients is 3 years, while only 7 months in T-PLL. Standard therapy of CLL with alkylating agents and prednisone have been not much effective in the treatment of PLL with a response rate of about 20%. Up to date no ideal treatment is available for PLL. A realistic goal is probably to achieve a clinical course transformation, from aggressive to mild, thus changing from short to long term prognosis. For this purpose the initial therapeutic approach cannot be limited to a single agent only. Splenic irradiation, intensive anthracyclines-based regimens, leukapheresis combine together represent the best therapeutic choice. Alkylating agents with or without prednisone may play a role in keeping indolent clinical course. Fludarabine has shown antileukemic activity against PPL even in patients resistant.

Combined Modality Therapy↗
PubMed1990

[Primary pulmonary lymphoma. Current data. Apropos of 9 cases].

The authors report 9 cases of primary pulmonary lymphoma (PPL). With this report, together with the publication of recent and important studies and with the latest advances in immunology, the principal features of this rare entity are emerging from among other lymphoproliferative pathologies of the lung. As a rule, PPL is a histologically well-differentiated tumour with low malignancy and slow course. Treatment is surgical in localized forms. In extensive forms there is no firmly established treatment, but the absence of clinical symptoms permits therapeutic abstention.

Adult↗