Local anesthesia with conscious sedation for laparoscopic intrafallopian transfer.

Local anesthesia with conscious sedation is well accepted by patients and provides scheduling flexibility, cost containment, patient safety, and ease of recovery. We believe the technique should be offered to selected patients undergoing intrafallopian transfer. By adhering to specific guidelines for surgical technique and monitoring, the procedure is a safe and acceptable alternative to general anesthesia for laparoscopic intrafallopian transfers.

Phase I trial of etoposide with cyclosporine as a modulator of multidrug resistance.

PURPOSE: To determine the maximum-tolerated dose (MTD) of cyclosporine (CsA) infusion administered with etoposide for 3 days in patients with cancer. PATIENTS AND METHODS: Of the 72 registered patients, 26 were treated initially with CsA and etoposide. Forty-six received etoposide alone until disease progression, and 31 of these proceeded to CsA and etoposide. CsA was administered as a 2-hour loading dose (LD) and as a 3-day continuous infusion (CI); doses were escalated from 2 to 8 mg/kg LD and 5 to 24 mg/kg/d CI. RESULTS: Fifty-seven patients were treated with 113 cycles of CsA with etoposide. Steady-state serum CsA levels (nonspecific immunoassay) more than 2,000 ng/mL were achieved in 91% of the cycles at CsA doses > or = 5 mg/kg LD and > or = 15 mg/kg/d CI. The major dose-related toxicity of CsA was reversible hyperbilirubinemia, which occurred in 78% of the courses with CsA levels > 2,000 ng/mL. Myelosuppression and nausea were more severe with CsA and etoposide. Other CsA toxicities included hypomagnesemia, 60%; hypertension, 29%; and headache, 21%. Nephrotoxicity was mild in 12% and severe in 2% of the cycles. Tumor regressions occurred in four patients after the addition of CsA (one non-Hodgkin's lymphoma, one Hodgkin's disease, and two ovarian carcinomas). Biopsy procedures for tumors from three of the four patients who responded were performed, and the results were positive for mdr1 expression. CONCLUSIONS: Serum CsA levels of up to 4 mumol/L (4,800 ng/mL) are achievable during a short-term administration with acceptable toxicities when administered in combination with etoposide. The CsA dose that is recommended in adults is a LD of 5 to 6 mg/kg, followed by a CI of 15 to 18 mg/kg/d for 60 hours. CsA blood levels should be monitored and the doses should be adjusted to achieve CsA levels of 2.5 to 4 mumol/L (3,000 to 4,800 ng/mL). Reversible hyperbilirubinemia may be a useful marker of inhibition by CsA of P-glycoprotein function. When used with high-dose CsA, etoposide doses should be reduced by approximately 50% to compensate for the pharmacokinetic effects of CsA on etoposide (Lum et al, J Clin Oncol, 10:1635-1642, 1992).

Regional myocardial blood flow and cardiac mechanics in dog hearts with CO2 laser-induced intramyocardial revascularization.

Laser-induced intramyocardial revascularization (LIR) has been used to promote direct communications between blood within the ventricular cavity and that of the existing myocardial vasculature in an attempt to increase perfusion in patients with ischemic heart disease. This study was conducted to measure the effects of LIR channels on regional myocardial flood flow (microspheres), cardiac mechanics (sonomicrometers), and myocardial tissue pressures in 18 dogs. Under baseline hemodynamic conditions (mean HR = 165.2 +/- 11.4 bpm, LVP = 123.6 +/- 22.9/4.0 +/- 1.8 mm Hg, AoP = 112.8 +/- 27.1/77.0 +/- 22.5 mm Hg), myocardial blood flow in laser-treated tissue (mean = 1.11 +/- .10 cc/min/gm before laser; .71 +/- .19 cc/min/gm after laser) was reduced as compared to blood flow in control tissue (mean = 1.12 +/- .15 cc/min/gm before laser; 1.25 +/- .22 cc/min/gm after laser). Regional myocardial systolic shortening (11.32% +/- 3.82% before laser; 7.49% +/- 2.86% after laser) was decreased by 33%. During simultaneous reversible ligation of the LAD and LCCA for 2 min, when intramyocardial channels represented the only tissue access for the injected microspheres, blood flow in laser-treated tissue was not increased above that of the control non-lasered tissue. However, regional blood flow was greater in laser-treated ischemic tissue (mean = .61 +/- .12 cc/min/gm) than in untreated ischemic areas (mean = .04 +/- .03 cc/min/gm) when left ventricular pressure (LVP) was acutely elevated (mean SLVP = 207.0 +/- 16.1 mm Hg). Using these measurements, a model is proposed to predict regional systolic pressure gradients between the left ventricular cavity and coronary intramyocardial vasculature required to permit restoration of blood flow to ischemic myocardium. We conclude that improved perfusion via laser-induced intramyocardial channels does not occur in otherwise normal myocardium exposed to acute coronary ligation and only small improvements in perfusion are noted when LVP is significantly elevated. Consideration of further clinical application of this approach is seriously cautioned awaiting additional experimental studies.

Public cholesterol screening: motivation for participation, follow-up outcome, self-knowledge, and coronary heart disease risk factor intervention.

We used a mailed questionnaire and telephone interviews with 1717 shopping center screenees whose total serum cholesterol was greater than 200 mg/dl. Our specific aim was to assess the subjects' motivations for participation in cholesterol screening, their follow-up outcome, their self-knowledge, and any coronary heart disease risk factor intervention. Of 1717 questionnaires mailed, 507 (30%) were returned; 64 of 100 subjects randomly selected for telephone interview could be contacted, and 61 were interviewed. Responses to the questionnaire and telephone interview were congruent, indicating little self-selection response bias. Before the cholesterol screening, 50% and 67% of questionnaire and telephone interview subjects knew their cholesterol levels. The nine most commonly cited reasons for cholesterol screening participation were: a desire to "watch" health (72%), convenience (70%), low cost (64%), to recheck previously measured total cholesterol (54%), publicity (34%), curiosity (30%), a relative with premature coronary heart disease (27%), the subjects' obesity (26%), and a relative's high cholesterol level (25%). As a result of cholesterol screening, 65% and 63% of questionnaire and telephone interview subjects, respectively, followed up with their doctors; 67% and 56%, respectively, had total cholesterol remeasured, but 17% and 18%, respectively, were told to "do nothing." At their doctors' follow-up, 74% and 51% of questionnaire and telephone interview respondents, respectively, began a low-saturated fat, low-cholesterol diet; 10% and 15% started taking a cholesterol-lowering drug. As a result of cholesterol screening, 76% and 85% of questionnaire and telephone interview subjects, respectively, changed their diets; 78% and 84% lowered their dietary cholesterol intakes, 62% and 74% increased their fiber intakes, 49% and 57% tried to lose weight, and 44% and 43% increased their exercise. Of questionnaire subjects, 94% thought that by lowering cholesterol, coronary heart disease risk could be reduced; 95% had become more aware of cholesterol in the last 5 years. Of telephone interview subjects, 91% concluded that cholesterol screening had motivated them to reduce cholesterol levels. Public cholesterol screening is convenient, inexpensive, facilitates self-knowledge about cholesterol, stimulates follow-up, and motivates physician and subject-guided dietary changes to reduce cholesterol levels and coronary heart disease risk.

In-vivo transperitoneal fertilization.

We present the technique of in-vivo transperitoneal fertilization (IVTPF) as a first approach to infertility treatment in couples with male subfertility or unexplained factors. The technique is statistically less successful but also less invasive than either gamete intra-Fallopian transfer (GIFT) or in-vitro fertilization - embryo transfer (IVFET) and offers considerable advantages over intrauterine insemination (IUI). The IVTPF technique involves transperitoneal transfer of processed spermatozoa within the pouch of Douglas after induction of ovulation. We report our 4-year experience with IVTPF which includes 136 treatment cycles in 89 couples. Eight pregnancies were achieved in 89 patients (9%) and 136 treatment cycles (7%). Fifty-one patients (57%) received IVTPF for only one treatment cycle; seven of the eight IVTPF pregnancies occurred in this group. An ectopic pregnancy resulted in one of the eight IVTPF pregnancies (13%). The functional quality of the sperm in those couples who achieved pregnancy was statistically superior to those couples who did not conceive. However, pregnancy was also obtained in case of severe oligozoospermia. Based on our experience, we feel IVTPF to be a very reasonable first approach in patients with no pelvic pathology and with infertility secondary to male factors or unexplained causes.

Know your cholesterol: population screening.

To facilitate the goal that all adult Americans know their total serum cholesterol levels, our specific aim was to evaluate the effectiveness, practicality, and cost of total cholesterol sampling in nonfasting self-referred subjects with use of venous blood and mailed results (n = 3844), and to compare these results with capillary blood total cholesterol levels (n = 1167), with immediate turnaround. We used consensus cut points of total cholesterol levels greater than 200, greater than 220, and greater than 240 mg/dl for moderate risk of coronary heart disease and greater than 220, greater than 240, and greater than 260 for high risk for aged 20 through 29, 30 through 39, and greater than 40 years. Total cholesterol level was in the moderate- or high-risk range in 45% and 37% of the venous and capillary cohorts, respectively. Median venous and capillary total cholesterol values were approximately 20 and 10 mg/dl greater than the total cholesterol values in the Lipid Research Clinics Prevalence Study, a difference contributed to by nonfasting versus fasting conditions, use of serum versus plasma, and self-referral bias for subjects with a family history of premature coronary heart disease. The cost per subject in the venous and capillary studies was $5.09 and $7.12 respectively, and $11.40 and $ 18.63 for each subject in the moderate- to high-risk range. Resampling with the subject fasting and follow-up were stressed, and were made available for moderate- and high-risk subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

A histologic study of laser-induced transmyocardial channels.

Carbon dioxide lasers are reported to provide ischemic myocardium direct access to blood within the ventricular cavity by inducing transmyocardial channels which maintain patency in long-term experiments. We have histologically examined the natural history of channels produced with this technique and compared them with transmyocardial channels created by needle puncture. Immediately after application of the laser, four concentric zones vaporization, carbonization, fixation, and transition could be distinguished along the transmyocardial path. Needle puncture channels were fully occluded within 48 hr, whereas laser-induced channels maintained partial patency for a 2-week period, after which they also became occluded. It appears likely that the instantaneous vaporization produced by the laser may delay the release of factors which mediate the healing process, but occlusion of channels was universal in this study. It remains to be determined whether or not variables such as wattage, beam diameter, or tissue temperature influence long-term channel patency.

NADH in situ laser fluorimetry: effect of pentobarbital on continuously monitored myocardial redox state.

NADH laser fluorimetry was applied to in situ monitoring of pentobarbital overload effect on myocardial redox state in rats. Experiments were carried out on open-chest rats anesthetized with pentobarbital. Use of very thin optical probes allowed measurements of NADH fluorescence directly within the myocardial wall. Quantitative analysis of fluorescent and backscattered light signals was made possible on-line. In 8 animals, a slow IV infusion of 6% pentobarbital (2 mg.min-1 for 10 min) induced an average twofold increase in NADH fluorescence, with constant return to baseline level prior to injection after a maximum period of 50 min. Thus, pentobarbital overload strongly affects the myocardial energetic state, and this effect was precisely evaluated with NADH fluorescence monitoring. In situ-monitored myocardial redox state variations during pentobarbital infusion can constitute a reference for similar studies on pharmacological agents aimed at protecting tissues against ischemic biochemical damages.