Biomedical subjects
G S Jones
Publications and source records attributed to G S Jones.
Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: phase I, 1981.
Thirty-one human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) ovulation induction cycles from 25 normally ovulating patients who applied to a program for the Vital Initiation of Pregnancy (VIP) are discussed. Three different categories of serum estradiol (E2) response were found. Serum E2 and progesterone responses were inversely related to the amount of hMG, indicating a patient sensitivity rather than a dosage relationship. Luteinizing hormone levels were suppressed by gonadotropins. Daily evaluation of vaginal smear, cervical mucus, serum E2 determinations, and pelvic ultrasound are necessary for an optimum ovulation induction with gonadotropins. Two successful pregnancies are reported.
Human menopausal gonadotropin/human chorionic gonadotropin follicular maturation for oocyte aspiration: phase II, 1981.
Ovulation was induced in 24 cycles of normal ovulatory patients for in vitro fertilization using a modified human menopausal gonadotropin and human chorionic gonadotropin (hMG/hCG) protocol. This modification was based on experience in 31 cycles previously studied. The individual ovarian threshold response to hMG seen previously was again confirmed, and successful stimulation and oocyte retrieval depended upon the recognition of this patient's "sensitivity." A rapid serum estradiol (E2) assay, in conjunction with estimation of the patient's biologic response to the E2 levels, as measured by changes in vaginal smears and cervical mucus (biologic estrogen shift), was the key to determining the amount of hMG necessary. The biologic shift was the best indicator for discontinuation of gonadotropins in the low E2 responder group. The serum E2 levels were the best indicators for the normal and high E2 responder groups. Ultrasound was used as confirmatory evidence for satisfactory follicular development. Postmaturity of the oocyte did not occur in this series, due to compensation of excessive hMG stimulation in rapid responders by a shortening of the interval between hMG discontinuation and hCG administration, thus initiating the oocyte meiotic process earlier. Maturation of immature oocytes was accomplished in this series by an increase in the time in culture prior to insemination. Due to the improved protocol of drug administration and the ability to mature immature oocytes in vitro, five pregnancies resulted from the stimulation of these 24 cycles.
Maturation and fertilization of morphologically immature human oocytes in a program of in vitro fertilization.
Oocytes of varying stages of maturity were aspirated from follicles primed with either human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) or a combination of follicle-stimulating hormone (FSH), hMG and hCG. Of the aspirated oocytes from 44 cycles, 74 were considered to be immature by virtue of morphologic characteristics of the oocytes and the degree of intercellular expansion of the associated cumular and membrana granulosa cells. After incubation periods of 22 to 35 hours in a Ham's F-10-based culture medium, these immature oocytes were inseminated with sperm donated by the patient's husband. Ultimately, 44 conceptuses were transferred to the respective uteri of 30 patients. Eight pregnancies were established as a result of these 30 transfers, two of which resulted from the transfer of only developed immature oocytes.
The importance of the follicular phase to success and failure in in vitro fertilization.
One hundred seventy-five cycles in patients with irreparable tubal disease were stimulated by human menopausal gonadotropin/human chorionic gonadotropin for the purpose of in vitro fertilization. As judged by the height of the peripheral estradiol response, the patients were classified as high, intermediate, or low responders. In addition, the estradiol pattern of the response was found to be separable into six categories. The pregnancy rate was found to be related to the height and to the pattern of peripheral response. The overall pregnancy rate in this consecutive series was 19% but varied according to the height and pattern of response from 40% to 0%.
What is a pregnancy? A question for programs of in vitro fertilization.
Pregnancy outcome in studies of normal reproduction and in programs of in vitro fertilization (IVF) is usually classified as "chemical beta-human chorionic gonadotropin (beta-hCG) abortion," "trimester abortion," and "term delivery." The distinction between a chemical beta-hCG abortion and a first-trimester abortion is not clearly stated in the literature, although such terms are commonly used. It is proposed that in programs of IVF pregnancy outcome be classified as "menstrual abortion," "preclinical abortion," "clinical abortion," or "viable pregnancy." Pregnancy outcome of 190 consecutive cycles induced by human menopausal gonadotropin/human chorionic gonadotropin in the program of IVF at Norfolk is compared with contemporary studies of pregnancy outcome in normal reproduction. The in vitro data indicate that the Norfolk program has recorded no menstrual abortions, a 33% preclinical and clinical abortion rate, and a viable pregnancy rate that approaches but does not equal the term delivery rate of normal reproduction. However, these results have been achieved by the transfer of multiple concepti, whereas normal reproduction depends on the fertilization of a single oocyte.
Serum luteinizing hormone during ovulation induction with human menopausal gonadotropin for in vitro fertilization in normally menstruating women.
Sixteen cycles in 14 normally menstruating women, stimulated with human menopausal gonadotropin in order to recruit more than one follicle for a successful in vitro fertilization process, were adequately monitored to identify the appearance of the spontaneous luteinizing hormone (LH) surge. Daily serum LH determinations, increased to every 4 hours in the presumptive preovulatory period, showed that in these women the endogenous estrogen-triggered LH midcycle peak did not occur at the expected time. It is hypothesized that the mechanism responsible for this suppression is a negative feedback mediated by an increased circulating protein with an inhibin-like action.
Decline of follicular oocyte maturation inhibitor coincident with maturation and achievement of fertilizability of oocytes recovered at midcycle of gonadotropin-treated women.
To examine whether a decline in follicular oocyte maturation inhibitor (OMI) is associated with attainment of oocyte maturation and fertilizability, OMI was measured in follicular fluid (FF) of 39 follicles of 20 normal women given human menopausal gonadotrophin and human chorionic gonadotrophin to induce follicular growth and maturation. Oocytes were aspirated per laparoscope, the fluid was saved, and the egg was observed, incubated, and inseminated with the husband's sperm. Concepti that developed to the 4- to 8-cell stage were transferred to the uterus and the women were followed for pregnancy. OMI activity in each FF was measured by using cultured cumulus-enclosed porcine oocytes (30-40 oocytes per FF sample). Estrogen, progesterone, oocytes (30-40 oocytes per FF sample). Estrogen, progesterone, and delta 4-androstenedione were measured in FF by radioimmunoassay. The FF of 13 preovulatory follicles yielding oocytes that were mature and fertilizable had significantly less OMI activity (mean +/- SEM) (0.58 +/- 0.10 unit/ml) compared to follicles yielding immature oocytes (2.8 +/- 0.56 units/ml; n = 9), atretic oocytes (5.5 +/- 2.5 units/ml; n = 7), or preovulatory oocytes with fractured zonae (1.9 +/- 0.63 units/ml; n = 7). The estrogen concentration (mean +/- SEM) of preovulatory follicles yielding mature fertilizable eggs or mature eggs with fractured zonae was greater (396 +/- 34 ng/ml; n = 20) compared to follicles yielding immature or atretic eggs (203 +/- 59 ng/ml; n = 9 and 97 +/- 47 ng/ml; n = 7, respectively; P less than 0.05). Progesterone concentration (mean +/- SEM; ng/ml) of FF was generally elevated in all preovulatory follicles (635 +/- 53) compared to immature or atretic follicles (230 +/- 64 and 76 +/- 17, respectively; P less than 0.05). It may be concluded that in normal follicle maturation there is a decline in OMI in the follicle containing an oocyte that becomes mature and fertilizable. There is also an increase in estrogen, progesterone, and follicle size. It is also possible to have an abnormal follicle maturation when there is an increase in size as well as FF, estrogen, and progesterone, but withut a decline in OMI--a situation which can lead to production of a nonfertilizable oocyte.
Fractures of the femoral shaft in a regional hospital setting.
We reviewed the efficacy of treatment techniques for femoral shaft fractures in our regional rural hospital setting. One hundred fifty consecutive primary femoral shaft fractures were managed at the Medical Center Hospital of Vermont during the period 1974 through 1979. The method of treatment was determined by the attending orthopedic faculty. Each case was evaluated at the time of initial hospital treatment, at 30 days postinjury, and at 1 year postinjury. Patient profiles, methods of injury, types of fracture, and associated injuries were reviewed. The choice of operative or nonoperative treatment in the first 30 days was the most important factor in the result at 1 year. Results were graded as "good' if angulation was 0-5 degrees in the A-P and/or lateral views; "fair', 6-10 degrees; and "poor', greater than 10 degrees or any need for supplemental surgery to achieve union. Shortening, infection, and thrombophlebitis were infrequent in this series. (formula: see text) Overall rate of supplemental surgery was 37% for the initially nonoperative treated femoral shaft fractures. In this series operative intervention gave surer results with an earlier return to full ambulation and more anatomic repair than nonoperative methods.
Transmembrane potential of isolated rat alveolar type II cells.
Type II cells were isolated from rat lungs by elastase digestion and purified by centrifugal elutriation. The fluorescent dye, Di-S-C3(5), was used as a probe to monitor transmembrane potential (Em) of cells suspended in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered medium. With this technique, the Em of type II cells was estimated to be -27 +/- 2 mV. This resting Em is very close to the equilibrium potential for chloride (-21 mV), which suggests that chloride is passively distributed in type II cells. The resting Em of type II cells is more dependent on the extracellular concentration of potassium (K+) than on external sodium (Na+); i.e., the membrane depolarizes as external sodium is replaced by potassium, suggesting that in unstimulated type II cells the membrane is more permeable to potassium than to sodium. In addition, the resting potential appears to be due, in part, to the activity of a ouabain-sensitive, Na-K pump, which acts to hyperpolarize type II cells. Addition of a membrane perturbant, phorbol myristate acetate (PMA, 10 micrograms/ml), to a type II cell suspension results in an increase in oxygen consumption and membrane depolarization. Both of these responses are sodium dependent and thus appear to be linked to a PMA-induced increase in sodium permeability.
Transport properties of isolated type II alveolar epithelial cells.
Type II cells are granular cells located in the alveolar epithelium. In addition to the synthesis and secretion of surfactant, these pneumocytes exhibit several other interesting properties. Although type II cells possess a high permeability to sodium, they maintain a low free intracellular sodium concentration by the presence of a Na-K pump. The activity of the Na-K pump is high and can result in substantial net movement of solute and water. Therefore, type II cells may employ this pumping capacity to play a significant role in the transepithelial transport of water. Type II cells are also relatively resistant to oxidant damage and play a role in the regeneration of the alveolar epithelium after oxidant injury. Ascorbate is a known antioxidant that is accumulated by type II cells via a specialized transport system for the uptake of ascorbate and sodium. The presence of this specialized transport system in type II cells and alveolar macrophages may explain in part why these cells are more resistant to oxidant injury than other pneumocytes.
Volcanic ash: toxicity to isolated lung cells.
Samples of volcanic ash from Mount St. Helens were collected from Spokane, Washington, after the major eruption of May 18, 1980. The toxicity of ash to the lung was estimated by monitoring the effects of in vitro and in vivo exposure on various physiological parameters of isolated lung cells. Volcanic ash had little effect on O2 consumption of rabbit type II pneumocytes, O2 consumption or superoxide release of resting rat alveolar macrophages, or membrane integrity of rat alveolar macrophages. Ash also caused no significant lipid peroxidation in rat lung microsomes. However, volcanic ash did inhibit superoxide anion release from zymosan-stimulated rat alveolar macrophages. Since superoxide is an antibacterial substance, this result suggests that exposure to volcanic ash may adversely affect the ability of alveolar macrophages to protect the lung from infection.
Ionic content and regulation of cellular volume in rat alveolar type II cells.
Alveolar type II epithelial cells were isolated by elastase digestion of rat lungs and purified by centrifugal elutriation. This method yields an enriched fraction of 1 x 10(7) cells/rat containing 85% pure type II pneumocytes. Purified type II cells exhibit a high rate of oxygen consumption, 215 nmol O2 . 10(6) cells-1 . h-1, which is unaffected by the addition of succinate. Type II cells contain 2 microliters H2O/10(7) cells and are approximately 325-330 micrometers 3 in volume. These pneumocytes contain 107 nmol K/l cell H2O and 70 mmol Cl/l cell H2O. In addition, type II cells have a high Na content, i.e., 156 mmol/l cell H2O. However, most of this Na is bound with only 33% being exchangeable. Therefore, the cytoplasmic concentration of free Na is 51 mmol/l cell H2O. Na uptake is very rapid and type II cells i.e., specific activity equilibrium is reached in 15 min with a half time of 5 min. In addition to this large passive transport of Na, type II cells exhibit a highly active Na-K pump involved in the regulation of cellular volume. Volume regulation is inhibited by a decrease in temperature (2 degrees C) and by the addition of ouabain (10(-4) M), Hg (10(-5) M), or Cu (10(-3) M).
Heartworms (Dirofilaria immitis) in coyotes (Canis latrans) in New England.
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The program for in vitro fertilization at Norfolk.
Several aspects of the program of in vitro fertilization (IVF), or, as it is called in Norfolk, the program for the Vital Initiation of Pregnancy (VIP), have been or are in the process of publication. However, because there has been no overall account, it seems appropriate to give a brief report of a general nature covering the period from the beginning of the effort in late February 1980 through December 31, 1981. Although minor changes were constantly made in the protocol, there were two major revisions. Therefore, a discussion of the program during three distinct periods, i.e., 1980, 1981-Phase I, and 1981-Phase II, is necessary. During 1980 and 1981 all patients had either no fallopian tubes or irreparable tubes.
Artificial insemination with fresh donor semen using the cervical cap technique: a review of 278 cases.
Two hundred twenty-six patients received artificial insemination with fresh donor semen (AID) using the cervical cap technique; 52 patients underwent the procedure for 2 conceptions. Using life-table analysis to adjust for uneven patient follow-up, the cumulative pregnancy rate was 62.5% after 6 months of AID, and 82.4% after 10 months. Moreover, using a mathematical model of cumulative pregnancy following AID, the estimated cure rate was not significantly different from 100%, and the estimated monthly probability of pregnancy among those cured was 15.5%. Age was found to be inversely related to pregnancy success, while parity had no effect. For those who continued to undergo AID beyond 6 months, the monthly probability of pregnancy did not decline. Patients can be advised that their chance of conception with AID should approach that of normal fertile couples.
Abnormal responses of granulocytes in chronic granulomatous disease.
Stimulation of normal granulocytes with chemotactic factor, phorbol myristate acetate, concanavalin A, and calcium ionophore results in rapid depolarization which precedes the 'respiratory burst'. Treatment of granulocytes in chronic granulomatous disease with these stimulants fails to generate chemiluminescence. This defect is associated with an absence of transmembrane potential shifts in response to treatment with chemotactic factor, phorbol myristate acetate, and concanavalin A while depolarization in response to A23187 is unaffected by this disease state.
Naproxen sodium, aspirin, and placebo in primary dysmenorrhea. Reduction of pain and blood levels of prostaglandin F2-alpha metabolite.
In a double-blind, crossover study of 32 women with primary dysmenorrhea, the analgesic efficacy of naproxen sodium was compared to that of aspirin and placebo. The treatment started 1 to 5 days before the onset of menses and continued for 3 to 5 days. At the same time, a radioimmunoassay established concentrations of 13,14-dihydro-15-keto-prostaglandin F2-alpha, a prostaglandin F2-alpha metabolite (PGF-M) in blood samples obtained from before the treatment and on the first day of menses. In affording pain relief, naproxen sodium was superior to aspirin (p = 0.02) and placebo (p = 0.002); however, aspirin was not superior to placebo (p = 0.05). During naproxen sodium treatment, the patients' daily activities were less impaired than during both the aspirin and the placebo treatment courses. During naproxen sodium treatment, the mean blood PGF-M levels decreased by 73.5%, from a mean of 50.5 to 13.4 pg/ml; during aspirin treatment they decreased by 31.2%, from a mean of 44.2 to 30.4 pg/ml; during placebo treatment, an increase of 13.6% was observed, from a mean of 46.3 to 52.6 pg/ml. The PGF-M decrease during the naproxen sodium treatment was significantly more prominent than that during both aspirin and placebo treatments (p = 0.0001). Changes caused by aspirin treatment were significantly different from those occurring during the placebo treatment (p = 0.001). The study confirms that at the doses utilized in this study the analgesic properties of naproxen sodium are superior to those of the more conventional prostaglandin synthetase inhibitor, aspirin, and that pain relief is related to the inhibition of prostaglandin synthesis.