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Biomedical subjects

J Porter

Publications and source records attributed to J Porter.

At least 199 records · Page 11Linked to original sources

Cuff-occluded rate of rise of peripheral venous pressure: a new, highly sensitive technique for monitoring blood volume status during hemorrhage and resuscitation.

We investigated the cuff-occluded rate of rise of peripheral venous pressure (CORRP)--a new, nearly noninvasive peripheral hemodynamic monitoring parameter--in dogs subjected to hemorrhage and resuscitation. Twelve adult mongrel dogs under general anesthesia were subjected to hemorrhage of 30% of their estimated total blood volume (TBV) for 30 minutes; after this time the extracted blood was reinfused. Arterial pressure (AP), central venous pressure (CVP), pulmonary arterial pressure (PAP), cardiac output (CO), pulmonary venous pressure (PWP), heart rate, and CORRP were continuously monitored. A "clinically significant change" (CSC) in CORRP and CO was defined as a change that exceeded two standard deviations from the mean of five baseline measurements made before the onset of hemorrhage, whereas a CSC in PWP or CVP was conservatively defined as a change that exceeded 2 mm Hg from the average of five baseline measurements, and a CSC in PAP and AP was defined as a change that exceeded 3 mm Hg and 5 mm Hg, respectively from the average of the baseline measurements. There was no consistent change in heart rate during hemorrhage. Thus defined, a CSC in CORRP occurred after an average extraction of 9.2% +/- 4.7% TBV, whereas a CSC was not seen until an average loss of 16.5% +/- 8.1% TBV for AP, 21% +/- 13% TBV for PWP, 15.5% +/- 7% TBV for PAP, and 35% +/- 3% TBV for CVP. These average blood losses are all significantly different from the average blood loss required to effect a CSC in CORRP. The blood loss required to effect a CSC in CO averaged 9.7% +/- 6%. We conclude that in these anesthetized dogs, CORRP detected blood loss earlier than other commonly used hemodynamic parameters, including several invasive parameters such as CVP, PAP, and PWP; CORRP and CO were equivalent in their ability to detect early stages of blood loss.

Animals↗

New effective gonadotropin releasing hormone antagonists with minimal potency for histamine release in vitro.

In order to minimize the adverse effect of histamine release in the rat of some gonadotropin releasing hormone (GnRH) antagonists, such as [Ac-D2Nal1,D4FPhe2,DTrp3,DArg6]-GnRH, new structures with modifications at positions 1, 2, 3, 5, 6, 7, and 10 were synthesized and tested in several biological systems. In vitro: the affinity for the pituitary GnRH receptor was measured as was the ability of the analogues to inhibit GnRH-stimulated release of luteinizing hormone (LH) by dispersed anterior pituitary cells in culture and to release histamine from rat mast cells. In vivo: inhibition of ovulation in the cycling rat was determined after subcutaneous (sc) injection of the peptides at noon on the day of proestrus; the duration of action of the peptides was evaluated by measuring LH levels in the castrated male rat after sc injection of some selected analogues. [Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,D-4-p-methoxy benzoyl-2-aminobutyric acid6,DAla10]-GnRH was found to be one of the most potent analogues of this series, causing a 100% inhibition of ovulation at 5 micrograms/kg or less. Release of histamine was observed at doses 10-25 times that required for [Ac-D2Nal1,D4FPhe2,DTrp3,DArg6]-GnRH. Thus, introduction of arginine in position 5 with a hydrophobic amino acid in position 6 is compatible with high potency in several biological systems and results in compounds with lowered potency to release histamine compared to homologous peptides with tyrosine in position 5 and D-arginine in position 6.

Animals↗

Immunological characteristics of purified pancreatic islet grafts.

In a DBA/2 (H-2d) pancreatic islet-to-B6AF1 (H-2b/k.d) recipient combination, the graft survival of hand-picked islets was compared with that of "crude digested" islets that were prepared simply by collagenase digestion and Ficoll gradient separation and were contaminated with lymph nodes and vascular and ductal tissue. Islet allografts were transplanted into the renal subcapsular space of streptozotocin-induced diabetic recipients. No immunosuppression was used. All the crude digested islet allografts were acutely rejected between days 7 and 18 with a median survival time (MST) of 10.2 +/- 2.5 days. In contrast, 33% (3/9) of the purified islet allografts survived more than 100 days. Simultaneous transplantation of purified islets and contaminating tissue resulted in a shorter graft survival (MST of 15.6 +/- 3.7 days). When 5 X 10(7) donor strain spleen cells were injected i.v. at the time of transplantation, all purified islet grafts were acutely rejected within 9 days. In addition, the rejection time of the purified islet allografts was inversely correlated with the number of donor spleen cells injected. These results indicate that contaminating tissues such as lymph nodes, vascular tissue, and ductal fragments present in the crude digested islet allografts are a major stimulus for induction of an immune response resulting in acute rejection of islet allografts.

Animals↗

The behavioral medicine unit: a community hospital model for inpatient treatment of adolescent depression.

This article describes one community hospital's response to the overwhelming needs of adolescents in central Iowa. It is based on the premise that many youths who have severe depression do not effectively respond to various outpatient counseling measures, and are in need of some type of inpatient treatment. Most such programs are locked psychiatric units run by child or adolescent psychiatrists. In our case, those wards already in existence are filled to capacity and cannot respond to outside needs. Placing these youth on traditional medical adolescent wards does not work, since medical staff are usually not geared to deal with the many, ever-changing mental health needs of these patients. Thus, we developed an unlocked adolescent inpatient unit with a pediatrician experienced in adolescent medicine as medical director; moreover, the program extensively utilizes psychologists, nurse-counselors, social worker-family therapists, recreation therapists, and other specialists. This program is a way for physicians trained in adolescent medicine and other appropriate persons to contribute to the complex health needs of youth; it is preferable to do this rather than send all depressed teenagers away by referrals, as seems to happen in some cases. It is also an important way for physicians and other specialists to demonstrate their expertise--both the Society for Adolescent Medicine and American Academy of Pediatrics have advocated such a demonstration--and to give physicians important training in the medical and mental health care needs of youth. Finally, the Spectrum Unit program provides a meaningful way for the primary care physician to be involved in the inpatient treatment of depressed adolescent patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Peptide N-alkylamides by solid phase synthesis.

Three new resins have been developed that allow for the solid phase synthesis of C-terminal peptide N-alkylamides using Boc amino acids, usual side chain protecting groups and hydrogen fluoride cleavage and deprotection. These resins were prepared by reacting the appropriate alkylamine (NH2CH3, NH2CH2CH3, NH2CH2CF3) to Merrifield's 1% divinylbenzene cross-linked chloromethylated polystyrene resin. The application of these resins to the synthesis of C-terminal GnRH N-alkylamides illustrates the versatility of this approach. GnRH analogs were tested for their ability to release LH from cultured rat anterior pituitary cells. [DGlu6, Pro9-NHCH2CH3]-GnRH was synthesized for the first time using the solid phase approach and found to be three times more potent than [DGlu6]-GnRH. Other analogs including [DTrp6, Pro9-NHCH2CH3]-GnRH, [DAla6, Pro9-NHCH2CF3]-GnRH and related peptides were found to be equipotent and to have the same properties (HPLC retention times, amino acid analysis and specific rotation) as the corresponding peptides synthesized using less amenable strategies; yields were equivalent or better than those reported earlier.

Animals↗

Periportal localization of lorazepam glucuronidation in the isolated perfused rat liver.

The relative effects of pretreatment with allyl alcohol and carbon tetrachloride on oxidative and glucuronide metabolism of lorazepam have been compared in the isolated perfused rat liver. Livers from rats pretreated for 24 hr with allyl alcohol (1.8 ml/kg, 1:50 solution, to induce pericentral hepatic necrosis), carbon tetrachloride (0.8 mg/kg in corn oil, to induce perivenular hepatic necrosis), or vehicle were perfused with 20% rat blood, 80% Krebs bicarbonate buffer at 20 ml/min. After 300 micrograms of lorazepam had been added to the reservoir, perfusate concentrations of lorazepam were measured in the perfusate at timed intervals. After 180 min, lorazepam and lorazepam glucuronide were measured in perfusate, bile, and liver homogenate. Allyl alcohol and carbon tetrachloride lowered lorazepam clearance by 47% and 77%, respectively. Recovery of lorazepam glucuronide after 180 min was lowered by 35% by treatment with allyl alcohol and increased 73% by treatment with carbon tetrachloride. Glucuronide recovery permitted estimation of fractional glucuronide vs. nonglucuronide clearance. In control rats, glucuronide clearance accounted for 25% of total clearance. Allyl alcohol caused a 64% reduction in glucuronide clearance but only a 39% reduction in nonglucuronide clearance. In contrast, carbon tetrachloride caused a 60% reduction in glucuronide clearance but an 83% reduction in nonglucuronide clearance. The differences in ratios of the changes in glucuronide and nonglucuronide clearance provide further circumstantial evidence that is consistent with the hypothesis of predominant periportal localization of glucuronidation and pericentral localization of oxidative metabolism of lorazepam.

Allyl Compounds↗

Contingent fees in medical malpractice litigation - a qualitative assessment.

The medical profession has experienced high liability insurance premiums accompanied by widespread use of contingent fees in medical malpractice litigation. It is worthwhile, therefore, to assess qualitatively the merits of contingent fees, the evidence suggesting that they are associated with unjustified litigation and their implications for the medical and legal professions.

Fees and Charges↗

Sexuality, fertility and contraception in disability.

In this review the authors describe ways in which particular disabilities may affect sexual performance, fertility, menstruation and pregnancy. The special contraceptive needs of people with various physical and mental disabilities are discussed, with each method of contraception being discussed together with its indications for use by people with various disabilities. The authors conclude that if family planning services are to be improved for people with disabilities, those providing the services must increase their awareness and acceptance of sexuality in disabled people.

Contraception↗

Carcinogenic epoxides of benzo[a]pyrene and cyclopenta[cd]pyrene induce base substitutions via specific transversions.

We have determined the spectrum of base-pair substitution mutations induced in the lacI gene of a uvrB- strain of Escherichia coli by two polycyclic aromatic hydrocarbons--(+/-)7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10 tetrahydrobenzo[a]pyrene (BPDE), and 3,4-epoxycylopenta[cd]pyrene (CPPE). Approximately 10% of all lacI mutations induced by either BPDE or CPPE are nonsense mutations, suggesting that base-pair substitutions are a large fraction of the mutational events induced by these agents in the uvrB- bacteria. Both carcinogens specifically induced the G . C leads to T . A and, to a lesser extent, the A . T leads to T . A transversions. One possible mechanism for transversion induction at G . C sites by BPDE might involve carcinogen binding to the exocyclic amino group of guanine in the template strand followed by a rotation of the modified base around its glycosylic bond from the anti to the syn conformation. This could allow specific pairing of modified bases with an imino tautomer of adenine.

Benzopyrenes↗