Blood loss and transfusion requirements in patients implanted with a mechanical circulatory support device undergoing cardiac transplantation.

Patients implanted with mechanical circulatory support devices (MCSD's) are at high risk for post-operative bleeding at cardiac transplantation. However, the magnitude of the risk and transfusion requirements for MCSD patients at the time of transplantation have not been previously reported. The purpose of this study was to characterize and compare the bleeding characteristics and transfusion requirements of 3 sub-groups of cardiac transplant patients: primary (n = 45), redo (n = 26), and MCSD (n = 23) patients.

Can spinal surgery be prevented by aggressive strengthening exercises? A prospective study of cervical and lumbar patients.

OBJECTIVE: To determine if patients recommended for spinal surgery can avoid the surgery through an aggressive strengthening program. SETTING: A privately owned clinic, staffed by physicians and physical therapists, that provides treatment for patients with neck and/or back pain. METHODS: Over a period of 2 1/2 years, consecutive patients referred to the clinic for evaluation and treatment were enrolled in the study if they (1) had a physician's recommendation for lumbar or cervical surgery, (2) had no medical condition preventing exercise, and (3) were willing to participate in the approximately 10-week outpatient program. Treatment consisted mainly of intensive, progressive resistance exercise of the isolated lumbar or cervical spine. Exercise was continued to failure, and patients were encouraged to work through their pain. Third-party payors in Minneapolis were surveyed for average costs. Average follow-up occurred 16 months after discharge. RESULTS: Forty-six of the 60 participants completed the program; 38 were available for follow-up and three required surgery after completing the program. DISCUSSION/CONCLUSIONS: Despite methodologic limitations, the results are intriguing. A large number of patients who had been told they needed surgery were able to avoid surgery in the short term by aggressive strengthening exercise. This study suggests the need to define precisely what constitutes "adequate conservative care."

Oxygenator anatomy and function.

The natural lung is the organ responsible for oxygen and carbon dioxide exchange between the blood and the outside environment. This function is accomplished by the large surface area and high permeability of the gas exchange interface, the alveolar-capillary membrane. These same features are fundamental to the design of an artificial lung, or oxygenator. Additional lung-like features essential to the design of an ideal oxygenator include the ability to achieve balanced oxygen and carbon dioxide exchange with minimal blood damage and blood activation. The purpose of this review is to present the past and current developments of the oxygenator designs in terms of the structural and functional features of the natural lung as well as the limitations in the ability to mimic the features of the lung because of the lack of appropriate technology.

The clinical effects of intensive, specific exercise on chronic low back pain: a controlled study of 895 consecutive patients with 1-year follow up.

Eight hundred ninety-five consecutive chronic low back pain patients were evaluated. Six hundred twenty-seven completed the program. One hundred sixty-one began, but dropped out, and 107 were recommended for treatment but did not undergo treatment for various reasons. Average duration of symptoms prior to evaluation was 26 months. Forty-seven percent of patients were workers' compensation patients. The primary treatment was intensive, specific exercise using firm pelvic stabilization to isolate and rehabilitate the lumbar spine musculature. Patients were encouraged to work hard to achieve specific goals. Seventy-six percent of patients completing the program had excellent or good results. At 1-year follow up 94% of patients with good or excellent results reported maintaining their improvement. Results in the control group were significantly poorer in all areas surveyed except employment.

Internucleosomal DNA fragmentation in ovine luteal tissue associated with luteolysis: in vivo and in vitro analyses.

Internucleosomal DNA fragmentation, a characteristic of apoptosis, can be visualized with agarose gel electrophoresis as discrete low-molecular-weight DNA fragments (laddering), in multiples of approximately 185 bp. CL were collected from superovulated ewes (control) or at 12 h after injection of prostaglandin F2 alpha (PGF2 alpha) on various days after hCG injection. The ability of PGF2 alpha on Days 8, 10, 12, and 14 (n > or = 3 per day per treatment) to induce luteal cell DNA fragmentation was evaluated. DNA was isolated and visualized on agarose gels. No DNA fragmentation was observed in CL from control ewes on Days 8, 10, or 12. Internucleosomal fragmentation of DNA (indicative of apoptosis) as well as nonspecific DNA fragmentation (indicative of non-apoptotic cell death) in CL from Day 14 controls was observed in two of four animals. Additionally, this pattern of DNA fragmentation was observed in CL from ewes treated with PGF2 alpha on all days. Evidence of DNA fragmentation was observed in luteal tissue after dissociation, yet no fragmentation was observed in unsliced, non-dissociated CL collected from Day 10 control ewes (incubated 4 h), or in sliced, non-incubated CL. Slicing and incubation alone were sufficient to initiate DNA fragmentation. A variety of approaches were utilized to inhibit DNA fragmentation. Only the addition of zinc acetate (1 mM) in the incubation medium throughout the 4-h incubation period prevented DNA fragmentation that was initiated by slicing (p < 0.05). There appear therefore, to be one or more intraluteal factors that directly initiate DNA fragmentation associated with cell death in luteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential regulation of Ca2+ homeostasis in ovine large and small luteal cells.

This study was undertaken to characterize differences in Ca2+ homeostasis between small and large ovine luteal cells. Although increasing extracellular pH (pHex) resulted in increases in intracellular calcium ([Ca2+]in) in both cell types, the large cells exhibited a greater sensitivity, suggesting that distinct [Ca2+]in regulatory mechanisms with distinct pH optima are operating in the two cell types. The sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase inhibitors thapsigargin (TG) and cyclopiazonic acid (CPA) increased [Ca2+]in in both cell types. Treatment of small cells with CPA resulted in transient increases in [Ca2+]in, whereas CPA produced sustained increases in [Ca2+]in in large cells. In small cells, pretreatment with CPA prevented further increases in [Ca2+]in in response to TG and vice versa. In large cells, TG pretreatment precluded further increases in [Ca2+]in with either prostaglandin F2 alpha (PGF2 alpha) or CPA. In contrast, after CPA pretreatment, PGF2 alpha or TG induced further increases in [Ca2+]in in large cells. This suggests that a TG-sensitive, CPA-insensitive Ca2+ pool is present in large cells but not in small cells. Neither Na+ removal nor KCl addition affected [Ca2+]in in either cell type, indicating that neither the Na+/Ca2+ exchanger nor voltage-dependent Ca2+ channels are involved in Ca2+ homeostasis in these cells. Addition of the calcium antagonist, LaCl3 (La3+), produced a gradual increase in [Ca2+]in in large cells but no changes in [Ca2+]in in small cells. Additionally, treatment with increasing concentrations of 4-bromo-A23187 resulted in titratable increases in [Ca2+]in that are greater in large than small cells, suggesting that small cells possess a higher Ca(2+)-buffering capacity than large cells. Progesterone secretion by large cells was significantly inhibited at alkaline pHex. In the presence of PGF2 alpha, progesterone secretion exhibited a distinct pH optimum of 7.0. In contrast, pHex did not affect secretion of progesterone in small cells under any of the conditions tested. TG, CPA, and La3+ all reduced secretion of progesterone in large, but not small, cells. These results demonstrate that ovine large and small luteal cells differ in regulation of [Ca2+]in homeostasis, and that treatments that increase [Ca2+]in decrease progesterone secretion in large cells but have no effect in small cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Prostaglandin F2 alpha releases calcium from a thapsigargin-sensitive pool in ovine large luteal cells.

Thapsigargin (TG) and A23187 were used to examine the regulation of cytosolic free calcium (Cai2+) in ovine large and small luteal cells. Thapsigargin (50 nM) induced a sustained increase of Cai2+ in fura 2-acetoxymethyl ester (AM)-loaded cells (large = 1.32 +/- 0.07-fold, small = 1.45 +/- 0.07-fold, P < 0.05). A23187 (1 microM) induced a rapid transient increase of Cai2+ (large = 1.37 +/- 0.07-fold, small = 1.46 +/- 0.10-fold, P < 0.05). In large cells, 0.5 microM prostaglandin F2 alpha (PGF2 alpha) increased Cai2+ 1.54 +/- 0.11-fold. Pretreatment with 50 nM TG abolished the PGF2 alpha-induced calcium response. Pretreatment with PGF2 alpha attenuated (P < 0.05) the TG-induced Cai2+ increase. Progesterone secretion was significantly (P < 0.05) inhibited by incubation with 50 nM TG, 1 microM A23187, and 0.5 microM PGF2 alpha in large but not small cells. These data suggest that PGF2 alpha releases calcium from a TG-sensitive intracellular calcium pool in ovine large luteal cells.

Treatment standards for work-related injuries.

Medical costs associated with treating work-related injuries have been steadily increasing, even faster than traditional medical care. Recent legislative investigation identified several injuries where medical costs were more than two times higher when the condition was work-related vs. non-work-related. In response, the 1992 Minnesota Legislature passed a broad-based Workers' Compensation reform package. One component of this legislative initiative was authorizing emergency rule-making power to develop treatment standards for several conditions which account for significant amounts of health care dollars. The treatment standard for low back pain and upper extremity disorders are described.

Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: II. Modulation of the transient and resting cytosolic free calcium alters progesterone secretion.

A previous study demonstrated that prostaglandin F2 alpha (PGF2 alpha) stimulates a transient increase in cytosolic free Ca2+ levels [( Ca2+]i) in ovine large luteal cells. In the present study, the magnitude of the PGF2 alpha (0.5 microM)-induced calcium transient in Hanks' medium (87 +/- 2 nM increase above resting levels) was reduced (P less than 0.05) but not completely eliminated in fura-2 loaded large luteal cells incubated in Ca2(+)-free or phosphate- and carbonate-free medium (10 +/- 1 nM, 32 +/- 6 nM, above resting levels; respectively). Preincubation for 2 min with 1 mM LaCl3 (calcium antagonist) eliminated the PGF2 alpha-induced calcium transient. The inhibitory effect of PGF2 alpha on secretion of progesterone was reduced in Ca2(+)-free medium or medium plus LaCl3. Resting [Ca2+]i levels and basal secretion of progesterone were both reduced (P less than 0.05) in large cells incubated in Ca2(+)-free medium (27 +/- 4 nM; 70 +/- 6% control, respectively) or with 5 microM 5,5'-dimethyl bis-(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (40 +/- 2 nM; 49 +/- 1% control; respectively). In addition, secretion of progesterone was inhibited (P less than 0.05) by conditions that increased (P less than 0.05) [Ca2+]i; that is LaCl3 ([Ca2+]i, 120 +/- 17 nM; progesterone, 82 +/- 8% control) and PGF2 alpha ([Ca2+]i, 102 +/- 10 nM; progesterone, 82 +/- 3% control). In small luteal cells, resting [Ca2+]i levels and secretion of progesterone were reduced by incubation in Ca2(+)-free Hanks ([Ca2+]i, 28 +/- 2 nM; progesterone, 71 +/- 6% control), however, neither LaCl3 nor PGF2 alpha increased [Ca2+]i levels or inhibited secretion of progesterone. The findings presented here provide evidence that extracellular as well as intracellular calcium contribute to the PGF2 alpha-induced [Ca2+]i transient in large cells. Furthermore, whereas an adequate level of [Ca2+]i is required to support progesterone production in both small and large cells, optimal progesterone production in large cells depends upon an appropriate window of [Ca2+]i.

Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: I. Alterations in cytosolic-free calcium levels and calcium flux.

The effect of prostaglandin F2 alpha (PGF2 alpha) on cytosolic calcium homeostasis was studied in suspensions of ovine large or small luteal cells from superovulated ewes. In large cells loaded with fura-2 (AM), resting cytosolic-free calcium ([Ca2+]i) was 62 +/- 5 nM (Hanks' medium, pH 7.15), and PGF2 alpha (0.5 microM) induced a rapid transient increase in [Ca2+]i to 152 +/- 6 nM, which then decreased to 97 +/- 6 nM within 3 min and remained at this level for the remainder of the treatment period (10-20 min). PGF2 alpha did not alter intracellular pH (pHi) in cells loaded with snarf-1 (AM) (pHi indicator). The transient nature of the [Ca2+]i increase was due, at least in part, to the ability of PGF2 alpha to stimulate (P less than 0.05) 45Ca2+ efflux. In small cells, resting [Ca2+]i was 57 +/- 5 nM, and no change in [Ca2+]i levels or pHi occurred with the addition of PGF2 alpha. PGF2 alpha also did not affect 45Ca2+ efflux in small cells. Calcium uptake was not significantly altered by PGF2 alpha in large or small cells. Data from kinetic analysis of the calcium transient was best fit to a two-compartment model consisting of a rapidly effluxing compartment and a slowly effluxing compartment. The size and rate constants were 62 +/- 10 nM and 3.6 +/- 1 min-1, respectively, for the rapidly effluxing compartment and 140 +/- 9 nM and 0.02 +/- 0.002 min-1, respectively, for the slowly effluxing compartment. These results provide evidence for a direct effect of PGF2 alpha specifically on the ovine large luteal cell that involves alterations in [Ca2+]i and calcium flux. This effect is likely to be involved in intracellular mediation of the signal for luteal regression.

Select cardiovascular and metabolic responses of diabetic rats to moderate exercise training.

The combined influence of diabetes and moderate treadmill exercise training on select metabolic and cardiovascular parameters was investigated with mature male Sprague-Dawley rats assigned to either control diabetic or diabetic groups receiving exogenous insulin. Experimental diabetes was induced with streptozotocin (80 mg.kg-1, i.v.) and verified by blood glucose concentrations greater than 16 mmol. The animals were designated as control, insulin-injected (5 U.kg-1, twice daily), or saline-injected (twice daily), and assigned to either non-trained or trained sub-groups. Insulin treatment partially restored the measured physiological functions to within normal limits. All animals were trained at 60 to 70% maximal oxygen consumption for 9 wk and exhibited higher maximal oxygen consumption values and cytochrome oxidase activity of the soleus muscles. Diabetes caused lower (P less than 0.05) reductions in resting heart rate but training-induced bradycardia did not occur in any group. Heart rate response to atropine sulfate (1 mg.kg-1, atrial choline acetyltransferase activity, atrial acetylcholine concentration, and quinuclidinyl benzilate binding was measured to evaluate changes in the parasympathetic nervous system. Atropine-induced cardiac acceleration was most pronounced in control and least effective in diabetic animals. Endurance training had no meaningful influence on this response to cholinergic inhibition. Quinuclidinyl benzilate binding for the diabetic and the diabetic groups receiving insulin revealed no change in receptor number, receptor affinity, or training effects. These findings indicated that 9 wk of exercise training improves the aerobic capability of insulin-deficient rats without changing cardiovascular characteristics associated with the parasympathetic nervous system.