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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 613 records · Page 34Linked to original sources
PubMed1991

Liver transplantation at the University of Pittsburgh, 1984 to 1990.

Patient and primary graft survival for 2,090 patients who received primary liver transplants at the University of Pittsburgh from 1984 through 1990 are presented. Observed (actual) 3- and 12-month patient and primary graft survival rates were compared for 3 periods: 1) January 1984 to September 1987 (cyclosporine, OKT3, and Euro-Collins preservation period); 2) October 1987 to December 1988 (University of Wisconsin solution preservation period); and 3) January 1989 to December 1990 (FK506 period). Data for results according to age group, medical urgency, and primary diagnosis are provided. In addition, estimated survivor and cumulative hazard functions (life-table method) for patient and primary graft survival out to 60 months after transplantation are presented. Overall results have improved significantly in recent experience. Most notable are the improved results seen in liver transplantation for patients with biliary atresia (especially in infants), primary sclerosing cholangitis, fulminant hepatic failure, and chronic active hepatitis B. For all but a few conditions, most of the mortality after liver transplantation occurred in the first 3 months after surgery. Less than 2% of patients were lost in each 6-month interval beyond the first 6 months after transplantation. Outcome was related to patient condition at the time of surgery. Observed survival rates at 3 and 12 months for patients called in the hospital to receive a transplant were 88.6% and 86.5%, respectively, compared with 81.9% and 73.7% for patients in critical condition. The continuing shortage of organs for transplantation, which often forces patients to wait longer for an organ than they can afford to, continues to impose a significant penalty.

Adolescent↗
PubMed1991

In-vivo pharmacokinetic characteristics of a transdermal phenylpropanolamine (PPA) preparation.

Phenylpropanolamine hydrochloride (PPA-HCL) is a synthetic phenylisopropanolamine sympathomimetic agent which is structurally related to ephedrine and amphetamine. Although its precise mechanism of action has not been conclusively determined, PPA is known to exert cardiovascular effects possibly related to indirect stimulation of beta-adrenergetic receptors in the heart. In addition, through CNS stimulation, PPA is known to act as an appetite suppressant, the anorexigenic effect being much weaker than that of amphetamine. In order to develop a convenient dosage of PPA, a transdermal preparation containing 250 mg PPA has been developed. Transdermal delivery is convenient both in terms of case of application and ready withdrawal of drug if desired. Oral PPA dosage forms are designed to have a fall off period of 6-8 hours to facilitate sleep. Such a drug free period is easily attained using a transdermal system either by removal of the transdermal device or incorporation of a lag period into the design of the system. The bioavailability and in vitro pharmacokinetic characteristics of this novel PPA preparation were compared with those of a reference sustained-release 75 mg Q16 PPA tablet (Acutrim), in a pilot, 3 subject, unblinded, cross-over, single dose study. Subjects fasted from the evening before dosing until 0.5 hours prior to dosing. Patches were removed 24 hours following application. Reportedly effective plasma PPA levels for appetite suppression were recorded after patch application and were comparable to those observed with the reference. Peak plasma PPA levels were slightly higher for the transdermal patch compared with the tablet formulation (93.6 ng/ml versus 80.10 ng/ml respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1991

Distal ileum and colon: targeted sites for 5-ASA release.

Sulphasalazine, used in the treatment of ulcerative colitis, is cleaved in the colon by the metabolic action of colonic bacteria on the diazo bond to release 5-Aminosalicylic acid (5-ASA) and sulpharidine. Whilst the former has been demonstrated to be active moiety, the latter is reputed to be responsible for toxicity associated with sulphasalazine therapy. A new multi-particulate formulation of 5-ASA has been designed (Asalan) to achieve targeted release of the drug in both the distal small intestine and colon and hence may be beneficial in the treatment of not only Ulcerative Colitis but also Crohn's disease. An imaging study was performed with beads formulated with barium sulphate using the same procedure employed to prepare 5-ASA beads. This study suggested 5-ASA capsule disintegration and bead dispersal in both the distal ileum and colon. This targetting was confirmed in two further in vivo studies using the 5-ASA formulation itself. In the first study comparison of plasma ASA levels following treatment with sulphasalazine treatment confirmed that 5-ASA release was occurring proximal to the colon. Despite this earlier release, the percentage of administered dose that was unabsorbed (dose-urinary recovery) was approximately 90%. In a second study a comparison was made with a single unit tablet of 5-ASA. A greater consistency and accuracy of targetting, as revealed by the appearance of plasma ASA levels, was confirmed for the capsule formulation. These separate studies were undertaken to evaluate the in vivo intestinal release characteristics of this new 5-ASA formulation in healthy volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1991

Dose proportionality of pharmacokinetics with a cr-verapamil formulation.

The relatively short half life of verapamil necessitates divided daily dosing in the treatment of angina, hypertension and arrhythmia. To reduce dosing frequency and increase patient compliance and therapeutic efficacy, a controlled-release once-daily verapamil formulation (Verelan) has been developed in three dosage strengths, 120 mg, 240 mg and 360 mg. In order to investigate the dose linearity of this formulation in the 120 mg and 360 mg dose range, un unblinded, crossover, comparative evaluation of the three dosage strengths was performed in a population of 27 male volunteers. Each treatment period lasted nine days with a minimum of 7 days between periods. On Days 1 and 2 of each treatment period, the single dose phase was evaluated following administration of medication on Day 1 only with regular blood sampling over the 48 hour period. On Days 3 and 7 inclusive, the five-day steady phase was evaluated. Mean plasma profiles following administration of each dose demonstrated extended verapamil absorption up to 24 hours after dosing. In both the single dose and steady state phases a linear relationship was observed between increasing dose and pharmacokinetic response over the dose range of 120 mg and 360 mg. This linearity in response with increasing dose is in contrast to the non-linearity of verapamil's pharmacokinetics with conventional verapamil formulations previously described by an number of workers and may be due to a saturation of verapamil's hepatic first pass metabolic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Pharmacokinetic characteristics of a novel controlled-release sprinkle formulation of salbutamol.

Childhood asthma, which commonly effects between 5 and 12% of children, is often treated with the beta agonist salbutamol which relaxes bronchial smooth muscle, resulting in bronchodilation. Although a popular mode of administration, delivery of salbutamol by aerosol is not often practical, particularly in younger children. A need therefore exists for a pediatric salbutamol dosage form, which not only controls asthma but is also convenient and acceptable to use. Enhanced control of asthma may be achieved using a controlled-release formulation of salbutamol. This also serves to increase patient compliance which may be further improved, in the case of children, by presenting the formulation in a more acceptable paediatric dosage form. In this study, a novel controlled-release sprinkle formulation of salbutamol was compared with a reference salbutamol tablet (Proventil Repetabs). This was conducted as a six subject unblinded, single-dose, cross-over study comparing a single dose (8 mg) of salbutamol sprinkle with a single dose (2 x 4 mg) of the reference tablet. The salbutamol sprinkle was formulated using the controlled-release polymeric micromatrix pharmaZome technology and was administered as a single dose dispersed in a spoonful of jam. The time to peak concentration, half-life and peak-to-trough ratio were similar for both formulations. Mean plasma salbutamol levels and mean peak salbutamol levels were slightly lower for the sprinkle formulation when compared with the reference. This novel sprinkle formulation has potential as an effective controlled-release bronchodilator which also offers distinct advantages for paediatric dosing, in terms of ease and acceptability of administration.

Albuterol↗
PubMed1991

[Anastomosis of free flaps to the inferior epigastric artery].

The inferior epigastric vessels are a reliable and easily accessible vascular pedicle for free tissue transplantation to the perineum, genital area, and the abdominal wall. Two cases serve to illustrate the procedure: the first involves a post-radiation ulcer following recurring carcinoma of the vulva with loss of the symphysis; the second involves a reconstruction of the abdominal wall employing a two-fold latissimus dorsi flap in a patient with malignant fibrous histiocytoma.

Abdominal Muscles↗
PubMed1991

The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats.

Translocation of enteric bacteria occurs in rats after hemorrhagic shock. A proposed mechanism involves intestinal mucosal injury by hypoperfusion. Recent work suggests that moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid. Seventy-eight Sprague-Dawley rats were anesthetized and subjected to 30 minutes of hemorrhagic shock (systolic blood pressure 30 to 50 mm Hg) through a modified Wigger's model. Resuscitation was performed with either shed blood (B), 3% HS + 1/2B (1:1), or with 7.5% HS + 1/2B (1:1). Spleen, liver, and mesenteric lymph nodes were sent for quantitative culture 24 hours later. Translocation occurred if enteric organisms were cultured from at least one organ. Statistical analysis used the Fisher exact test. Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7.5% hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion.

Animals↗
PubMed1991

Long-term overproduction of collagen in radiation-induced fibrosis.

Collagen metabolism was investigated in the fibrotic tissue which developed in pig thigh muscle 6 to 15 months after acute gamma irradiation. During this period, total collagen deposits in the fibrotic tissue increased 10-fold compared to the healthy muscle tissue. These deposits were composed mainly of type I and III collagen, and the type I/type III ratio was lower in the fibrotic than in the muscle tissue. Small pieces of both fibrotic and muscle tissue were incubated with [14C]proline. The [14C]hydroxyproline content of the fibrotic tissue reflected large concomitant increases in the synthesis of total collagen, mainly of types I and III, which rose 14- and 17-fold, respectively. Similarly, the level of type I and type III procollagen mRNAs rose 9- and 5-fold, respectively, in the fibrotic tissue versus the muscle tissue. These results suggest that procollagen gene transcription or RNA maturation in the cell nuclei is activated in the fibrotic tissue. The possibility that such activation is due to the long-term inflammatory state of this tissue is discussed.

Animals↗
PubMed1991

Phase II study of carboplatin in advanced breast cancer: preliminary results.

The antitumor activity of carboplatin (400 mg/m2 intravenously every 4 weeks) in advanced breast cancer was evaluated in two consecutive trials enrolling patients with and without prior exposure to chemotherapy, respectively. All patients had measurable disease in at least one site. The first trial included patients who had received prior chemotherapy (adjuvant, neoadjuvant, or chemotherapy for metastatic disease). All but one of these patients had previously received doxorubicin-containing combinations. There were no objective responses among the first 14 evaluable patients, although 7 of them had stable disease, including 2 with minor responses. The second trial, carried out with patients who had no prior exposure to chemotherapy, is ongoing. Currently, 6 of 19 evaluable patients have obtained a complete (1) or partial (5) response to carboplatin, resulting in an overall response rate of 32%. In both studies, toxicity was mild, mainly consisting of emesis (88%), leukopenia (22%), and thrombocytopenia (12%). Thus, by standard criteria, carboplatin was not found to be active in breast cancer patients with prior exposure to chemotherapy. Preliminary results in patients without such exposure are encouraging, although additional patients are needed to confirm these data.

Adult↗