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Biomedical subjects

A G McLeod

Publications and source records attributed to A G McLeod.

At least 19 recordsLinked to original sources

Loss of factor VIII activity during storage in PVC containers due to adsorption.

Recombinant factor VIII concentrates are stable when administered in a reconstituted form according to the manufacturer's specifications, and undiluted via infusion with syringe mini-pumps. However many Haemophilia centres administer recombinant factor VIII further diluted in intravenous fluids for greater ease of administration. To investigate the stability of recombinant factor VIII during administration as a diluted infusion, reconstituted factor VIII was stored in polyvinylchloride (PVC) mini-bags undiluted (146 IU mL-1) and at factor VIII concentrations of 10 IU mL-1 and 2 IU mL-1. After 48 h of storage at room temperature in PVC mini-bags, the recoveries of factor VIII activity were 41.9% of the initial activity for the undiluted (146 IU mL-1) product and 43.7% of the initial activity for factor VIII diluted to 10 IU mL-1. For factor VIII diluted to 2 IU mL-1, the amount of factor VIII activity remaining at 48 h was only 1.8% of the initial activity. In contrast, 100% of factor VIII activity was recovered after 48 h when undiluted reconstituted product (146 IU mL-1) was stored in a syringe. To investigate the mechanism of factor VIII activity loss during storage, factor VIII samples collected after 0, 3 and 48 h of storage were analysed by immunoblotting with factor VIII antibodies. No evidence of factor VIII proteolytic degradation during storage was found, however, large amounts of factor VIII antigen were recovered from the empty PVC mini-bags following elution with denaturing detergent. We conclude that clinically significant losses of factor VIII activity occur during storage in PVC mini-bags and that the loss of activity is most likely due to protein adsorption onto the plastic surface. This loss of factor VIII activity during storage in PVC containers may substantially affect the safety and potential cost savings of administering recombinant factor VIII by continuous infusion.

Adsorption↗

Frog cardiac calsequestrin. Identification, characterization, and subcellular distribution in two structurally distinct regions of peripheral sarcoplasmic reticulum in frog ventricular myocardium.

Calsequestrin is a calcium-binding protein known to sequester calcium accumulated in the sarcoplasmic reticulum (SR) of muscle cells during relaxation. In the present study, we used affinity-purified antibodies to chicken cardiac calsequestrin to identify a 60,000-Da calsequestrin in frog myocardium. Like previously identified cardiac calsequestrins, it is enriched in cardiac microsomes, it is enriched by biochemical procedures previously used to purify cardiac and skeletal calsequestrins, and it exhibits a pH-dependent shift in its apparent Mr on a two-dimensional gel system. Finally, the NH2-terminal amino acid sequence of this 60,000-Da immunoreactive protein purified by fast protein liquid chromatography was identical to that of rabbit skeletal and canine cardiac calsequestrin. Thus, we conclude that this protein corresponds to the calsequestrin isoform in frog ventricular muscle. Frog calsequestrin was localized in discrete foci present at the periphery but absent from the central regions of frog ventricular myocytes as determined by immunofluorescence labeling. Immunoelectron microscopic labeling demonstrated that calsequestrin was confined to the lumen of two structurally distinct regions of the SR, where it was localized in the subsarcolemmal region of the myofibers. One of these appeared to correspond to the terminal SR previously reported to be closely apposed to the sarcolemma of frog myofibers. The other region, although close to the sarcolemma, was not physically joined to it and appeared to correspond to corbular SR. It generally is believed that frog cardiac SR does not provide activator Ca2+ required for excitation-contraction coupling. However, the identification of a calsequestrin isoform very similar to mammalian cardiac calsequestrin that is confined to specialized regions of frog cardiac SR lends support to the idea that frog cardiac SR has the ability to store Ca2+ and thus function in some capacity in frog cardiac muscle contraction.

Amino Acid Sequence↗

Evaluation of surgical staples in cesarean section.

Experience with Lactomer absorbable surgical staples (Auto Suture Poly CS 57 disposable surgical stapler) in 62 cesarean sections was compared with an equal number of operations performed with standard techniques. The technique of application of the stapler evolved with experience. Countertraction to staplers with Allis' clamps prevented uterine V incisions. Operative time was longer for the stapled suture group for primary cesarean sections, but was unchanged for repeat procedures. Excellent hemostasis of the uterine incision was achieved even when varicose sinusoidal veins were present. Significant reductions of hemoglobin deficits from 2.16 to 1.31 gm/dl, postoperative anemia from 29% to 6.4%, and endometritis from 22.5% to 6.4% occurred respectively in nonstapled and stapled groups. A reduced hospital stay, shortened by 2.1 days, saved each patient +F42950. Blood loss estimates by surgeons or anesthetists were often at variance. Surgeons' acceptance of the procedure grew with experience. On the basis of these results, use of absorbable staples offers certain advantages in reducing blood loss, infection, and hospital stay in cesarean deliveries.

Adult↗

Prospective pricing system by diagnosis-related groups: comparison of federal diagnosis-related groups with high-risk obstetric care groups.

Of 468 diagnosis-related groups identified by the federal government for Medicaid reimbursement, 15 are related to obstetric hospital care. Each diagnosis-related group is considered a distinct group in which cases are homogeneous with respect to resource consumption. Because the diagnosis-related group system is based primarily on data from community and secondary care hospitals, it does not differentiate sufficiently among high-risk obstetric patients seen at tertiary care institutions, such as Florida's Regional Perinatal Intensive Care Centers. We developed an alternative scheme for diagnosis-related groups, called obstetric care groups, using the federal diagnosis-related groups as the model from which to depart. Data collected for 4192 women during a 2 1/2-year period indicate that obstetric care groups provide more homogeneous groups than diagnosis-related groups for our population of high-risk patients. The obstetric care groups differentiate between no complications, one complication, and two or more complications, while the diagnosis-related groups differentiate only between no complications and one or more complications. Also, complications for obstetric care groups are based on only 19 diagnoses that contribute significantly to resource consumption, while the list of possible complications exceeds 200 for diagnosis-related groups. Although the obstetric care group classification system is simpler than that for diagnosis-related groups, it results in a more accurate reimbursement of hospitalization charges for high-risk obstetric care.

Diagnosis-Related Groups↗

A birth center affiliated with the tertiary care center: comparison of outcome.

A matched pair study compares 250 low risk women delivered in a tertiary care center with a similar group cared for and delivered in an affiliated birth center. The patients could be matched in every respect with the exception of educational background. Twenty-one percent of the birth center patients required transfer to the hospital during the intrapartum period. Differences were found in cervical dilatation upon admission and length of labor. Intermittent fetal heart auscultation was used exclusively in birth center mothers, oral fluids and light diet were allowed. The hospital group received intravenous fluids. Oxytocin augmentation was used twice as often, and the incidence of shoulder dystocia appeared significantly higher in the control group. The reasons for transfer are described. The one neonatal death was due to persistent fetal circulation.

Adolescent↗

Evidence for the presence of calsequestrin in both peripheral and interior regions of sheep Purkinje fibers.

Localization of calsequestrin in sheep Purkinje fibers was determined by indirect immunofluorescence labeling of cryostat sections of sheep myocardium from the intraventricular wall. The results presented show that calsequestrin is present in discrete foci at the peripheral, as well as the interior regions of the cytoplasm. Since Purkinje fibers lack transverse tubules, the presence of calsequestrin at specific foci in the interior regions of the cytoplasm in these cells suggests that calsequestrin is localized in the lumen of peripheral junctional sarcoplasmic reticulum, as well as in the lumen of corbular sarcoplasmic reticulum present in the I band region of the myofibrils. Assuming that the function of calsequestrin is to sequester calcium into the lumen of the sarcoplasmic reticulum, these results imply that two structurally different regions of the sarcoplasmic reticulum function as calcium storage sites in mammalian Purkinje fibers and raises the possibility that calcium storage and/or release from these two sites might be regulated differently.

Animals↗

Vaginal delivery after cesarean section.

The incidence of cesarean scar rupture varies from 0.64 to .24 per cent, with some institutions reporting no ruptures. Associated maternal mortality is extremely low, especially in low segment transverse incisions, so as to be almost nonexistent. Maternal mortality from cesarean section is higher than from vaginal delivery. Fetal mortality as a result of low segment scar rupture is at most 12.5 per cent. With modern methods of monitoring this should be reduced to zero. Several authors already report no fetal mortalities. Patients who have had a previous cesarean section should be allowed an attempt to deliver vaginally based on carefully selected criteria. Their labors should be followed closely by a qualified individual and are expected to follow norm-progressive course. The intrauterine cavity should be explored postpartum for defects. The cost of hospital care to the family is considerably reduced, and hospital bed utilization improved by allowing vaginal deliveries of women who have had previous cesarean sections, because of decreased operative risks, postpartum morbidity, and shorter hospital stays. The recovery period for the patient who delivered vaginally will generally be considerably reduced. Each subsequent pregnancy in which vaginal delivery is contemplated must be screened and managed as though it were her first after a section. Physicians should not charge different fees for elective repeat cesarean section versus vaginal delivery of the previous cesarean. Allowing a trial of labor in carefully selected patients is one step toward decreasing the cesarean section rate.

Cesarean Section↗

Carcinoma of the cervix among women in their twenties. A 14% prevalence deserves our respect!

The purpose of this study was to estimate the value of routine vaginal cytology in women under 30 years of age. Over a five-year period, 18,160 vaginal cytological examinations were made on women aged 20 through 29 years, and 424 women (2.3%) were found to have Papanicolaou smears class III, IV, or V. Of these 424 patients, 122 (28.8%) were found to have carcinoma of the cervix. A tissue diagnosis of intraepithelial carcinoma was obtained in 103 women. The remaining 19 patients proved to have invasive carcinoma of the cervix. Approximately one third of this group of women with positive cytology failed to return for tissue diagnosis so the true prevalence of cancer was probably in the region of 40%. The findings suggest that women deserve routine vaginal cytological examinations irrespective of age.

Adolescent↗

Familial Evans syndrome: a report of an affected sibship.

PURPOSE: This report describes the clinical course of three siblings, all of whom had Evans syndrome in childhood. PATIENTS: The coexistence of autoimmune hemolytic anemia and thrombocytopenia, in the absence of a known underlying cause, led to the diagnosis of Evans syndrome in a 4-month-old girl and subsequently in her two brothers when they were 4 and 13 years old. RESULTS: The 4-month-old girl had a life-threatening relapsing course unresponsive to corticosteroids, intravenous gamma-globulin, thymectomy, and cyclophosphamide. She eventually responded to splenectomy. Her two brothers had milder disease that responded to corticosteroids. Cytogenetic analyses revealed the presence of a familial Y;15 translocation in all three children and their father. CONCLUSION: There are few reported cases of familial Evans syndrome, and they are usually associated with an inherited congenital abnormality. We report the unusual finding of three siblings with the disease and no known congenital abnormality.

Adolescent↗