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Effects of emphysema on diaphragm blood flow during exercise.

Chronic hyperinflation of the lung in emphysema displaces the diaphragm caudally, thereby placing it in a mechanically disadvantageous position and contributing to the increased work of breathing. We tested the hypothesis that total and regional diaphragm blood flows are increased in emphysema, presumably reflecting an increased diaphragm energetic demand. Male Syrian Golden hamsters were randomly divided into emphysema (E; intratracheal elastase 25 units/100 g body wt) and control (C; saline) groups, and experiments were performed 16-20 wk later. The regional distribution of blood flow within the diaphragm was determined by using radiolabeled microspheres in hamsters at rest and during treadmill exercise (walking at 20 feet/min, 20% grade). Consistent with pronounced emphysema, lung volume per unit body weight was greater in E hamsters (C, 59.3 +/- 1.8; E, 84.5 +/- 5.0 ml/kg; P < 0.001) and arterial PO2 was lower both at rest (C, 74 +/- 3; E, 59 +/- 2 Torr; P < 0.001) and during exercise (C, 93 +/- 3; E, 69 +/- 4 Torr; P < 0.001). At rest, total diaphragm blood flow was not different between C and E hamsters (C, 47 +/- 4; E, 38 +/- 4 ml . min-1 . 100 g-1; P = 0.18). In both C and E hamsters, blood flow at rest was lower in the ventral costal region of the diaphragm than in the dorsal and medial costal regions and the crural diaphragm. During exercise in both C and E hamsters, blood flows increased more in the dorsal and medial costal regions and in the crural diaphragm than in the ventral costal region. Total diaphragm blood flow was greater in E hamsters during exercise (C, 58 +/- 7; E, 90 +/- 14 ml . min-1 . 100 g-1; P = 0.03), as a consequence of significantly higher blood flows in the medial and ventral costal regions and crural diaphragm. In addition, exercise-induced increases in intercostal (P < 0.005) and abdominal (P < 0.05) muscle blood flows were greater in E hamsters. The finding that diaphragm blood flow was greater in E hamsters during exercise supports the contention that emphysema increases the energetic requirements of the diaphragm.

Animals↗

Effect of severe isolated unilateral and bilateral diaphragm weakness on exercise performance.

Patients with isolated diaphragm paralysis depend on recruitment of extradiaphragmatic respiratory muscles to increase ventilation, but little is known about exercise performance or the response of the inspiratory muscles to loaded breathing. By convention, unilateral diaphragm paralysis is regarded as a trivial condition whereas bilateral paralysis is considered to be potentially life-threatening. In fact, no data exist concerning exercise performance under these conditions. We studied incremental treadmill exercise performed by eight patients with bilateral diaphragm paralysis, eight patients with unilateral diaphragm paralysis, and eight age-matched control subjects. Respiratory muscle endurance (RME) was also measured by an inspiratory threshold loading method. Exercise time, compared with control subjects (671 seconds), was moderately reduced in unilateral diaphragm paralysis (512 seconds, p = 0.07) and further reduced in bilateral diaphragm paralysis (456 seconds, p = 0.02). Similarly, peak minute ventilation was lower in patients with unilateral diaphragm paralysis (84 L x min(-1), p = 0.01) and in patients with bilateral diaphragm paralysis (69 L x min(-1), p = 0.001) compared with control subjects (114 L x min(-1)). However, patients with unilateral diaphragm paralysis and patients with bilateral diaphragm paralysis had increased ratios of peak oxygen consumption to peak minute ventilation compared with control subjects (p = 0.0007 and p < 0.0001, respectively). Nine patients had normal RME; exercise time was moderately increased in these patients (502 seconds) compared with seven patients with reduced RME (461 seconds). In conclusion, although exercise performance is impaired in bilateral diaphragm paralysis, these patients can sustain a reasonable exercise load, particularly if RME is preserved and compensatory mechanisms have developed. In addition, exercise tolerance is diminished in patients with unilateral diaphragm paralysis.

Adult↗

The diaphragm with and without spermicide. A randomized, comparative efficacy trial.

OBJECTIVE: To determine the relative contraceptive efficacy of a diaphragm used with spermicide as compared to one used without. STUDY DESIGN: Two hundred sixteen women entered the study between September 1985 and December 1990. Of these, 84 were randomly assigned to the diaphragm-only group and 80 to the diaphragm-with-spermicide group as their primary method of contraception. In addition, a spermicide-only group was planned originally to serve as a control group to assess the contribution to efficacy made by a spermicide alone. Thirty-nine women were randomly assigned to this group, and 13 selected themselves for it. All were followed for a maximum of 12 months. The primary outcome variable was accidental pregnancy. The statistical difference between the two diaphragm groups was analyzed. RESULTS: The 12-month "typical use" failure rates for the diaphragm-only group were 28.6 per 100 women and for the diaphragm-with-spermicide group, 21.2. The 12-month cumulative consistent-use failure rates were 19.3 per 100 women for the diaphragm-only group as compared to 12.3 per 100 women for users of a diaphragm with spermicide. CONCLUSION: Although the consistent use rates were not significantly different, this study had low statistical power and hence gives no support to the hypothesis that adjunctive spermicide use fails to improve the effectiveness of the diaphragm method, especially in view of the magnitude and direction of the difference observed. Unless a study with sufficient power proves that the use of a diaphragm alone is statistically as effective as use of a diaphragm with spermicide, use of a spermicide in conjunction with the diaphragm continues to be the appropriate clinical recommendation.

Adolescent↗

The effect of esophageal and gastric distension on the crural diaphragm.

BACKGROUND: The mechanism of prevention of gastric reflux into the esophagus is not exactly known. The lower esophagus has a barrier function provided by the lower esophageal sphincter. We investigated the hypothesis that the crural diaphragm shares in the barrier function not only mechanically but also actively through a crural-esophageal-gastric reflex action. METHODS: The study was performed during repair of abdominal ventral and incisional hernias in 20 subjects (11 men, 9 women; age 38.6+/-4.8 years). The electromyographic response of the crural diaphragm to individual balloon distension of esophagus and stomach was recorded by means of a needle electrode inserted into the crural diaphragm and connected to an electromyographic apparatus. The recordings were repeated after separate crural, esophageal, and gastric anesthetization. RESULTS: The crural diaphragm exhibited basal motor unit action potentials, which decreased on esophageal distension (P<0.001) after a mean latency of 17.3+/-2.8 SD ms. The crural diaphragm response to esophageal distension did not occur after the crural diaphragm or esophagus was anesthetized. Gastric distension effected an increase of crural diaphragm electromyographic activity with a mean latency of 18.4+/-4.6 ms; this effect could not be achieved after the crural diaphragm or stomach was anesthetized. CONCLUSIONS: The crural diaphragm has a resting tone that relaxes after esophageal distension and contracts after gastric distension. This sphincter-like action of the crural diaphragm appears to be a reflex and is mediated through the esophagocrural inhibitory and gastrocrural excitatory reflexes. The crural diaphragm seems to share actively in the gastroesophageal competence mechanism.

Action Potentials↗

Age-related changes in enzyme activity in the rat diaphragm.

Limited data exist concerning the effect of growth and aging on the metabolic properties of the diaphragm. Therefore, we investigated age-related changes in protein concentration and glycolytic and Krebs cycle enzyme activity in the diaphragm as well as the plantaris muscle of female Sprague-Dawley rats ranging in age from 1 to 12 months. Samples from the costal and crural diaphragm and the plantaris muscle were obtained from 38 animals in the following age groups: (1) 1 month old (N = 7); (2) 4 month old (N = 6) (3) 6 month old (N = 13); and (4) 12-month-old (N = 12). Body weight and diaphragm weight increased rapidly by a factor of 6 and in parallel during 1-4 months postpartum before reaching a plateau at 6 months of age. No significant difference (P greater than 0.05) existed in the ratio of diaphragm weight to body weight among age groups. Protein concentration was significantly higher (P less than 0.05) in the costal diaphragm and plantaris at 4 and 6 months when compared to 1 and 12 months of age. In the crural diaphragm, protein concentration was significantly lower (P less than 0.05) at 1 month postpartum when compared to all other age groups. Succinate dehydrogenase (SDH) activity was significantly higher (P less than 0.05) at 1 month of age in the plantaris, the costal diaphragm and the crural diaphragm when compared to older animals. In contrast, the activity of lactate dehydrogenase (LDH) in the plantaris, the costal diaphragm and the crural diaphragm was significantly lower (P less than 0.05) in the 1-month-old animals when compared to all other ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Surgical treatment of diaphragm disease correlates with improved survival in optimally debulked advanced stage ovarian cancer.

BACKGROUND: Diaphragm involvement by ovarian cancer is often considered to be a major obstacle to successful cytoreductive surgery. Lack of evidence of survival benefit, concerns over safety and lack of experience are common justifications for this belief. In this study, we sought to evaluate the therapeutic value of diaphragmatic surgery in advanced ovarian cancer. METHODS: Relevant data from all consecutive patients with stage IIIC and IV epithelial ovarian cancer, primarily operated at Mayo Clinic from 1994 through 1998, were collected and analyzed. Statistical analyses were performed using chi(2) test, Cox regression model and Kaplan-Meier curves including log rank test. For comparison of trends in performing procedures, an additional 91 consecutive patients undergoing surgery from August 1, 2002 and August 31, 2004 were analyzed. RESULTS: 244 eligible patients were identified. Mean age was 64 years (range: 24-87), and 5-year overall survival (OS) was 31.5%. For the entire cohort, residual disease (RD) was the only independent prognostic factor in multivariate analysis (P < 0.0001) when considering other factors including demographic, intraoperative findings and procedures performed. For the subgroup of patients with tumor involving the diaphragm (N = 181), patients who underwent diaphragm surgery (stripping of the diaphragmatic peritoneum, full or partial thickness diaphragm resection, excision of nodules or CUSA) had improved 5-year OS relative to those that did not (53% vs. 15%; P < 0.0001). Furthermore, in multivariate analysis of patients with diaphragm disease, both RD and performance of diaphragm surgery were independent predictors of outcome (P < 0.001). Considering the subgroup of patients with RD < 1 cm, we noted a strong survival advantage for those patients who underwent diaphragm surgical procedures (5-year survival: 55% vs. 28%; P = 0.0005). Over time, we noted a statistically significant increase in the rate of diaphragm procedures for patients with diaphragm involvement from 1994-98 relative to 2002-3 (22.5% vs. 40%: P = 0.022). CONCLUSIONS: Surgical procedures to treat diaphragm disease increase the rate of complete and optimal debulking and correlate with improved survival even compared to patients optimally debulked without diaphragm surgery performed.

Adult↗

Incidence and management of pleural effusions after diaphragm peritonectomy or resection for advanced mullerian cancer.

OBJECTIVES: Diaphragm peritonectomy or resection is an effective way to cytoreduce diaphragm disease but frequently results in sympathetic pleural effusions. Our objective was to determine the incidence and management of effusions that developed after diaphragm surgery in patients with advanced mullerian cancer. METHODS: We reviewed the records of all patients with stage IIIC-IV epithelial ovarian, fallopian tube, or peritoneal cancer who had diaphragm peritonectomy or resection as part of optimal primary cytoreduction at our institution from 2000-2003. All patients had preoperative and serial postoperative chest X-rays to detect and follow pleural effusions. Factors evaluated included the presence and size of preoperative and postoperative effusions, their laterality, and subsequent need for thoracentesis and/or chest tube placement for symptomatic effusions. RESULTS: Of the 215 patients who had primary cytoreduction during the study period, 59 (27%) underwent diaphragm peritonectomy or resection. In addition to standard cytoreduction, 31 (53%) of these 59 patients had diaphragm surgery alone, while 28 (47%) had diaphragm surgery in combination with other upper abdominal resections. Laterality of diaphragm surgery was as follows: right only, 43 (73%); left only, 2 (3%); and bilateral, 14 (24%). Intraoperative chest tubes were placed in 7 (12%) patients. In the remaining 12 patients with preoperative effusions, postoperative effusions on the same side as the diaphragm surgery increased in 6 patients (50%), and 3 patients (25%) required postoperative thoracentesis or chest tube. In the remaining 40 patients without preoperative effusions, ipsilateral effusions developed in 24 patients (60%), and 5 patients (13%) required postoperative chest tubes. The overall rate of new or increased ipsilateral effusions was 58%; the overall rate of postoperative thoracentesis or chest tube placement was 15%. In 75% of the patients, thoracentesis or chest tubes were placed within 5 days of surgery (median, 3 days; range, 2-24). CONCLUSIONS: More than half of patients developed ipsilateral pleural effusions after diaphragm peritonectomy for cytoreduction. Most were managed conservatively without requiring a chest tube or thoracentesis. The incidence of symptomatic effusions was not high enough to recommend routine chest tube placement at the time of diaphragm peritonectomy or resection.

Adult↗

Determination of ventilatory liver movement via radiographic evaluation of diaphragm position.

PURPOSE: To determine the accuracy of estimation of liver movement inferred by observing diaphragm excursion on radiographic images. METHODS AND MATERIALS: Eight patients with focal liver cancer had platinum embolization microcoils implanted in their livers during catheterization of the hepatic artery for delivery of regional chemotherapy. These patients underwent fluoroscopy, during which normal breathing movement was recorded on videotape. Movies of breathing movement were digitized, and the relative projected positions of the diaphragm and coils were recorded. For 6 patients, daily radiographs were also acquired during treatment. Retrospective measurements of coil position were taken after the diaphragm was aligned with the superior portion of the liver on digitally reconstructed radiographs. RESULTS: Coil movement of 4.9 to 30.4 mm was observed during normal breathing. Diaphragm position tracked inferior-superior coil displacement accurately (population sigma 1.04 mm) throughout the breathing cycle. The range of coil movement was predicted by the range of diaphragm movement with an accuracy of 2.09 mm (sigma). The maximum error observed measuring coil movement using diaphragm position was 3.8 mm for a coil 9.8 cm inferior to the diaphragm. However, the distance of the coil from the top of the diaphragm did not correlate significantly with the error in predicting liver excursion. Analysis of daily radiographs showed that the error in predicting coil position using the diaphragm as an alignment landmark was 1.8 mm (sigma) in the inferior-superior direction and 2.2 mm in the left-right direction, similar in magnitude to the inherent uncertainty in alignment. CONCLUSIONS: This study demonstrated that the range of ventilatory movement of different locations within the liver is predicted by diaphragm position to an accuracy that matches or exceeds existing systems for ventilatory tracking. This suggests that the diaphragm is an acceptable anatomic landmark for radiographic estimation of liver movement in anterior-posterior projections for most patients.

Diaphragm↗

The natural history of untreated penetrating diaphragm injury: an animal model.

BACKGROUND: Surgical repair of diaphragm injuries is rather straightforward, but diagnosis can be difficult. The natural history of diaphragm injury is quite controversial. Undoubtedly, many diaphragmatic injuries are missed at the initial evaluation. Some theories state that diaphragm injuries do not heal, and that all eventually lead to herniation. Current theories regarding uniform herniation of all diaphragm injuries are not supported by animal models. The authors developed a penetrating diaphragm injury model to study the natural history of this injury. METHODS: This study used 48 male Sprague-Dawley rats weighing 300-425 g. During the study, 24 of the rats received a 16-gauge needle puncture of the left diaphragm mimicking a small penetrating wound, whereas 24 of the rats received an injury produced with a 2.7-mm aortic punch, which created a defect comparable to a much larger penetrating wound. Half of the animals in each group were euthanized at 1 month, and the other half at 10 months. This allowed short- and long-term follow-up of the injuries. Gross inspection of the left diaphragm was performed after the animals were sacrificed via a thoracoabdominal incision. All diaphragms then were removed for examination. RESULTS: All the rats experienced perioperative recovery. None of the 24 rats with a 16-gauge needle injury had an injury at 1 month (n = 12) or 10 months (n = 12). No patent injury was noted in the aortic punch injury group (n = 12) sacrificed at 1 month. At 10 months, 1 of 12 animals had a small hepatic herniation through the aortic punch injury. All the injuries displayed adhesions to the underlying left hepatic lobe. CONCLUSIONS: The authors developed a penetrating diaphragm injury model to understand better the natural history of this injury. Spontaneous healing occurred in 98% of the animals. In this animal model, because the left lobe of the liver is present beneath the left diaphragm, healing without herniation usually occurs. A role may exist for nonoperative treatment of human right diaphragm injuries in clinical practice. This animal model may prove useful in further defining future management for these injuries.

Animals↗

Effects of the supine and prone position on diaphragm thickness in healthy term infants.

BACKGROUND: The physiological basis underlying the decline in the incidence of sudden infant death syndrome (SIDS) associated with changing the sleep position from prone to supine remains unknown. AIMS: To evaluate diaphragm thickness (t(di)) and shortening in healthy term infants in the prone and supine positions in order to determine whether changes in body position would affect diaphragm resting length and the degree of diaphragm shortening during inspiration. METHODS: In 16 healthy term infants, diaphragm thickness at the level of the zone of apposition on the right side was measured using ultrasonography. Heart rate (HR), breathing frequency (f), and transcutaneous oxyhaemoglobin saturation (SaO(2)) were recorded simultaneously during diaphragm imaging with the infants in the supine and prone positions during quiet sleep. RESULTS: At end expiratory (EEV) and at end inspiratory lung volumes (EIV), t(di) increased significantly in the prone position. The change in t(di) during tidal breathing was also greater when the infant was prone. SaO(2), HR, and f were not significantly different at EEV and at EIV in both positions. CONCLUSION: In healthy term infants, placed in the prone position, the diaphragm is significantly thicker and, therefore, shorter, both at EEV and EIV. Diaphragm shortening during tidal breathing is greater when the infant is prone. In the prone position, the decreased diaphragm resting length would impair diaphragm strength, and the additional diaphragm shortening during tidal breathing represents added work performed by the diaphragm. This may compromise an infant's capacity to respond to stressful situations when placed in the prone position and may contribute to the association of SIDS with prone position.

Algorithms↗

Effect of norepinephrine on diaphragm contractility and blood flow.

Recent studies have shown that diaphragm fatigue can be reversed by mechanical augmentation of phrenic arterial flow. The purpose of the present experiment was to determine whether it was possible to pharmacologically augment diaphragm blood flow and reverse fatigue by the administration of norepinephrine. Four groups of studies were performed, all employing our previously described in situ isometric canine diaphragm strip preparation (Supinski et al., J. Appl. Physiol. 60: 1789-1796, 1986). Group I studies examined the effects of norepinephrine on the contractility of the nonfatigued diaphragm in normotensive dogs, group II studies examined the effects of this drug on the contractility of the fatigued diaphragm in normotensive animals, and group III studies examined the effect of this drug on the contractility of the fatigued diaphragm in hypotensive animals. Group IV studies examined the effect of norepinephrine in normotensive animals in which the phrenic artery was cannulated and pump perfused at constant flow. Fatigue was induced in group II, III, and IV studies by rhythmically stimulating the diaphragm via intramuscular electrodes. Norepinephrine had no effect on the contractility of the nonfatigued diaphragm (group I). In normotensive (group II) and hypotensive animals (group III), norepinephrine elicited dramatic increases in arterial blood pressure and phrenic arterial flow and produced a significant upshift in the force-frequency curve of the fatigued diaphragm. However, when phrenic flow was held constant (group IV experiments), norepinephrine failed to augment the contractility of the fatigued diaphragm. These results indicate that 1) norepinephrine can increase phrenic blood flow and augment the contractility of the fatigued diaphragm in both normotensive and hypotensive conditions and 2) this effect of norepinephrine to partially reverse fatigue is secondary to its action to augment diaphragmatic blood flow.

Animals↗

Systolic ventricular dysfunction causes selective diaphragm atrophy in rats.

In order to examine the relative impairment of the diaphragm and other skeletal muscles in systolic ventricular dysfunction (VD), their structure and function were compared between rats with VD induced by left coronary artery ligation (n = 17) and sham-operated rats (Co, n = 10). In addition, in an attempt to unravel the mechanism of the observed impairment, we examined alterations in insulin-like growth factor-I (IGF-I) serum levels and IGF-I expression in the liver, diaphragm, and gastrocnemius. In a second series of rats (VD, n = 5 and Co, n = 5) hemodynamic measurements were performed. All measurements were performed 3 mo after the operation. Infarct size averaged 32 +/- 10 and 44 +/- 20% in the two series, respectively (NS). Hemodynamic measurements revealed a decrease in left ventricular peak systolic pressure of 19% (p < 0. 05). Significant diaphragm atrophy (weight: 622 +/- 52 mg in VD versus 750 +/- 54 mg in Co, p < 0.0005), without alterations in diaphragm contractile properties was present in VD animals. For all animals combined, the reduction in diaphragm weight was related to infarct size (r = -0.74, p < 0.001). No alterations were observed in the other inspiratory and peripheral muscles. ATPase staining of the diaphragm showed atrophy of type I and type IIx/b fibers, their cross-sectional area (CSA) being reduced by 13 and 16%, respectively (p < 0.05). There were no signs of myopathic alterations. IGF-I expression was increased by 55% in the diaphragm of rats with VD (p < 0.05). IGF-I expression in the liver and gastrocnemius and serum IGF-I levels were unaltered. These data suggest the presence of compensatory mechanisms aimed at minimizing diaphragmatic fiber atrophy. We conclude that systolic VD caused: (1) selective diaphragm atrophy, which was related to infarct size; (2) a decrease in diaphragm type I and IIx/b CSA not associated with myopathic changes; (3) an increase in the IGF-I mRNA content of the diaphragm. The selective diaphragm involvement in the present study may be related to the moderate degree of ventricular dysfunction induced.

Adenosine Triphosphatases↗

Increased injury and intramuscular collagen of the diaphragm in COPD: autopsy observations.

Evidence for diaphragm injury in people with chronic obstructive pulmonary disease (COPD) has been reported, although the extent of injury and collagen accumulation post mortem have not previously been examined. In addition, it is not known whether the amount of injury and collagen are different in key regions of the diaphragm. The cross-sectional area of collagen and the percentage of abnormal myofibres in the post mortem diaphragm and psoas major were determined by computer-assisted image analysis of stained cross-sections of the diaphragm for collagen with picrosirius red and with haematoxylin and eosin for morphology. In the midcostal diaphragm of six subjects with COPD and six subjects with no significant respiratory disease, the COPD diaphragm displayed a greater cross-sectional area of collagen and percentage of abnormal myofibres (collagen: 24.2+/-1.0 versus 18.6+/-1.1%; injury: 28.4+/-7.2 versus 12.0+/-1.3%). In 18 patients with various respiratory conditions, the midcostal diaphragm displayed more collagen and abnormal myofibres than the crural diaphragm, while both costal and crural diaphragms displaying more collagen and abnormal myofibres than psoas major. This study reveals extensive injury and collagen accumulation in the chronic obstructive pulmonary diseased diaphragm, and reveals a regional pattern of injury and intramuscular collagen which may correspond to variations in diaphragm loading.

Analysis of Variance↗

Nonspermicide fit-free diaphragm trial reported.

The standard technique of diaphragm fitting and the use of spermicide with diaphragms have been challenged by Edward Stim, a physician who developed and tested a nonspermicide fitfree disphragm (NFFD) method. He suggested that the main cause of diaphragm failure was erratic use, and that occasional nonuse was a result of the irritations caused by overly large diaphragms, the messiness of spermicides, and the need to anticipate intercourse in order to place the diaphragm in advance. From 1974-79, Stim prescribed the Koroflex diaphragm with a rim diameter of 60 mm for all his patients requesting diaphragm contraception. He believed the 1 size produced "an efficient sperm-blocking obstruction in virtually all women." Stim deemphasized spermicide use while carefully instructing the women on correctdiaphragm placement and advising continual use of the device. He reported a high rate of effectiveness for a barrier method, with 1.1 pregnancies/100 woman-years of use. Failure rates ranging from 2-19% have been reported for users of conventional diaphragms with spermicide. In 1981, the Marie Stopes House in London undertook a study to determine the failure rate for the NFFD as compared to that reported for the conventional diaphragm, to ascertain acceptability of NFFD to women and their partners, and to determine whether NFFD offered significant practical advantages for service delivery. Family Health International assisted in the analysis of data. The incidence of pregnancy in the Marie Stopes study was much higher than had been previously reported. A total of 39 (35.5%) of the women remained in the study discontinued use of the NFFD within a 12-month period, 20 (18.2%) because they become pregnant. Of 110 women enrolled in the trial, 22 (20%) were lost to follow-up. The 2nd most common reason for termination of NFFD use was "personal reasons," including lack of confidence in the method. In spite of the reported pregnancy rate of 24.1/100 women at 12 months, a high level of acceptability of the NFFD was demonstrated among the women who had used it successfully. In fact, 48 (43.6%) women refused to discontinue use of the method even after being told of the high risk of pregnancy. Although the diaphragm is a proven contraceptive method, research remains to be done in this area. The NFFD study was not able to distinguish whether lack of fit or nonuse of spermicides caused the failures. A next step may be a small controlled trial of fitted diaphragms with and without spermicides.

Birth Rate↗

Sponge versus diaphragm for contraception.

BACKGROUND: The contraceptive vaginal sponge was developed as an alternative to the contraceptive diaphragm. The sponge, made of polyurethane impregnated with nonoxynol-9 (1g), releases 125 mg of the spermicide over 24 h of use. Unlike the diaphragm, the sponge can be used for more than one coital act within 24 h without the insertion of additional spermicide, and the sponge does not require fitting or a prescription from a physician. How the sponge compares with the diaphragm in terms of efficacy and continuation is not clear. OBJECTIVES: To compare the efficacy and continuation rates of the sponge compared with the diaphragm (used with nonoxynol-9 as a spermicide). Our a priori hypothesis was that the sponge would have a higher failure rate and higher discontinuation rates than the diaphragm. SEARCH STRATEGY: We searched the computerized databases MEDLINE, EMBASE, Popline, LILACS, and the Cochrane Controlled Trials Register. In addition, we searched the reference lists of all potentially relevant articles and book chapters. We also contacted investigators involved with both trials identified to seek other published or unpublished trials. SELECTION CRITERIA: We included randomized controlled trials comparing the vaginal contraceptive sponge (Today; Collatex) with any diaphragm used with nonoxynol-9 to prevent pregnancy. DATA COLLECTION AND ANALYSIS: We examined the studies identified through the literature searches for possible inclusion and evaluated their methodological quality using the Cochrane guidelines. We contacted an author involved with both published trials for supplementary information about randomization and allocation concealment. We entered data into RevMan 4.1 and calculated Peto odds ratios for overall pregnancy and 12-month discontinuation using numbers of women as the denominator. We also abstracted 12-month cumulative life-table ratios for these same outcomes, but were unable to aggregate these data. MAIN RESULTS: The sponge was statistically significantly less effective in both trials in preventing overall pregnancy than was the diaphragm. The 12-month cumulative life-table termination rates per 100 women for overall pregnancy were 17.4 for the sponge versus 12.8 for the diaphragm in the larger U.S. trial and 24.5 for the sponge and 10.9 for the diaphragm in the U.K. trial. Similarly, discontinuation rates at 12 months were higher with the sponge than with the diaphragm (odds ratio 1.3; 95% CI 1.1-1.6). Allergic-type reactions were more common with the sponge in both trials, although the frequency of discontinuation for discomfort differed in the two trials. REVIEWER'S CONCLUSIONS: The sponge was less effective than the diaphragm in preventing pregnancy. Discontinuation rates were higher at 12 months as well. Other randomized controlled trials will be needed to resolve the role of spermicides in preventing sexually transmitted infections or in causing adverse effects.

Contraceptive Devices, Female↗

Acceptability of an existing, female-controlled contraceptive method that could potentially protect against HIV: a comparison of diaphragm users and other method users.

OBJECTIVE: The diaphragm, an internal barrier contraceptive device, is a candidate for a female-controlled method for preventing human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This study's objective was to examine how women who use the diaphragm differ from women using the pill and/or condoms with respect to factors hypothesized to influence the acceptability of contraceptive methods. Our goal was to increase understanding of who finds the diaphragm acceptable and why. METHODS: We conducted a cross-sectional telephone survey with selected female members of a managed care organization. For this analysis, we limited the sample to 585 women currently using the diaphragm (n = 196), pill (n = 200), condoms (n = 132), or pill and condoms (n = 57). We conducted bivariate analyses and multinomial logistic regression analyses to assess the associations between selected characteristics and diaphragm use. RESULTS: Diaphragm use was significantly associated with several variables. Of particular interest, placing less importance on hormonal method characteristics was significantly associated with diaphragm use (versus use of the pill, condoms, or both). Placing more importance on barrier method attributes was significantly associated with diaphragm use (versus pill use, alone or with condoms). In addition, lower condom use self-efficacy was significantly associated with diaphragm use (versus condom use, alone or with pill). Lack of motivation to avoid HIV/STIs was significantly associated with using the diaphragm versus condoms (only). CONCLUSION: These results have important implications for future research, interventions, counseling strategies for providers, and product development. Our findings suggest that if the diaphragm protects against HIV, it could be a desirable option for some women.

Adolescent↗

PV1 is a key structural component for the formation of the stomatal and fenestral diaphragms.

PV1 is an endothelial-specific integral membrane glycoprotein associated with the stomatal diaphragms of caveolae, transendothelial channels, and vesiculo-vacuolar organelles and the diaphragms of endothelial fenestrae. Multiple PV1 homodimers are found within each stomatal and fenestral diaphragm. We investigated the function of PV1 within these diaphragms and their regulation and found that treatment of endothelial cells in culture with phorbol myristate acetate (PMA) led to upregulation of PV1. This correlated with de novo formation of stomatal diaphragms of caveolae and transendothelial channels as well as fenestrae upon PMA treatment. The newly formed diaphragms could be labeled with anti-PV1 antibodies. The upregulation of PV1 and formation of stomatal and fenestral diaphragms by PMA was endothelium specific and was the highest in microvascular endothelial cells compared with their large vessel counterparts. By using a siRNA approach, PV1 mRNA silencing prevented the de novo formation of the diaphragms of caveolae as well as fenestrae and transendothelial channels. Overexpression of PV1 in endothelial cells as well as in cell types that do not harbor caveolar diaphragms in situ induced de novo formation of caveolar stomatal diaphragms. Lastly, PV1 upregulation by PMA required the activation of Erk1/2 MAP kinase pathway and was protein kinase C independent. Taken together, these data show that PV1 is a key structural component, necessary for the biogenesis of the stomatal and fenestral diaphragms.

Animals↗

Acceptability of the vaginal diaphragm among current users.

CONTEXT: Interest in the diaphragm has been growing, in part because it is a female-controlled method that might protect against HIV and other sexually transmitted diseases (STDs). A better understanding of diaphragm acceptability is needed. METHODS: In 2001-2002, female members of a managed care organization were interviewed by telephone. The 215 participants, aged 19-49, who reported diaphragm use during the past three months were asked about their experience with the method and background characteristics. Characteristics associated with women's satisfaction with and consistent use of the diaphragm were identified through multiple logistic regression analysis. RESULTS: Most participants had a low risk for HIV and other STDs. The mean duration of diaphragm use was 8.5 years. Although only 42% of participants reported consistent use in the past three months, most were satisfied with the method (79%) and planned to use it at next vaginal intercourse (85%). Satisfied users had significantly higher diaphragm use self-efficacy and more positive perceptions of the method than those not satisfied. Consistent use was significantly associated with older age and having had some college education rather than none. More than half of women cited dissatisfaction with previous methods (72%) and provider recommendation (61%) as moderately to extremely important in their decision to begin diaphragm use. When asked what they would change about the diaphragm, 32% mentioned concerns related to inserting or removing it. CONCLUSIONS: From an acceptability point of view, the diaphragm appears to be a viable candidate for a female-controlled method for prevention of HIV and other STDs. Our findings have important implications for the reintroduction of the traditional diaphragm and development of new diaphragm-like products.

Adult↗