New Research Aims to Optimize Therapy Against Onchocerciasis.

Onchocerciasis is a parasitic disease that is the second most common cause of infectious blindness in the world, affecting 25 million people, mostly in sub-saharan Africa. Mass drug administration (MDA) with ivermectin has been the mainstay of a successful international effort to reduce the burden of vision loss. Despite improvements in infection rates and blindness through MDA with ivermectin, adult worms are not killed or permanently sterilized by this drug and can live for greater than 10 years. Therefore, new treatments for onchocerciasis are critical to accelerating the rate of elimination of this blinding disease. Here we discuss an ongoing study of a new treatment for onchocerciasis.

Attenuated hypothalamic responses to α-melanocyte stimulating hormone during pregnancy in the rat.

KEY POINTS: Increased appetite and weight gain occurs during pregnancy, associated with development of leptin resistance, and satiety responses to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) are suppressed. This study investigated hypothalamic responses to α-MSH during pregnancy, using c-fos expression in specific hypothalamic nuclei as a marker of neuronal signalling, and in vivo electrophysiology in supraoptic nucleus (SON) oxytocin neurons, as a representative α-MSH-responsive neuronal population that shows a well-characterised α-MSH-induced inhibition of firing. While icv injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, supraoptic, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, this response was suppressed in pregnant rats. Similarly, SON oxytocin neurons in pregnant rats did not demonstrate characteristic α-MSH-induced inhibition of firing that was observed in non-pregnant animals. Given the known functions of α-MSH in the hypothalamus, the attenuated responses are likely to facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy. ABSTRACT: During pregnancy, a state of positive energy balance develops to support the growing fetus and to deposit fat in preparation for the subsequent metabolic demands of lactation. As part of this maternal adaptation, the satiety response to the anorectic peptide α-melanocyte stimulating hormone (α-MSH) is suppressed. To investigate whether pregnancy is associated with changes in the response of hypothalamic α-MSH target neurons, non-pregnant and pregnant rats were treated with α-MSH or vehicle and c-fos expression in hypothalamic nuclei was then examined. Furthermore, the firing rate of supraoptic nucleus (SON) oxytocin neurons, a known α-MSH responsive neuronal population, was examined in non-pregnant and pregnant rats following α-MSH treatment. Intracerebroventricular injection of α-MSH significantly increased the number of c-fos-positive cells in the paraventricular, arcuate and ventromedial hypothalamic nuclei in non-pregnant rats, but no significant increase was observed in any of these regions in pregnant rats. In the SON, α-MSH did induce expression of c-fos during pregnancy, but this was significantly reduced compared to that observed in the non-pregnant group. Furthermore, during pregnancy, SON oxytocin neurons did not demonstrate the characteristic α-MSH-induced inhibition of firing rate that was observed in non-pregnant animals. Melanocortin receptor mRNA levels during pregnancy were similar to non-pregnant animals, suggesting that receptor down-regulation is unlikely to be a mechanism underlying the attenuated responses to α-MSH during pregnancy. Given the known functions of α-MSH in the hypothalamus, the attenuated responses will facilitate adaptive changes in appetite regulation and oxytocin secretion during pregnancy.

Intraoperative management of posterior capsular rupture.

PURPOSE OF REVIEW: Posterior capsular rupture (PCR) and vitreous loss are inevitable complications encountered in cataract surgery across all levels of surgical experience and in spite of technological advances to improve safety. Thus, cataract surgeons must always be prepared to practice safe and effective intraoperative management strategies for capsular rupture. RECENT FINDINGS: Novel approaches for lens fragment removal, vitrectomy, and lens implantation have expanded the available options for cataract surgery in the setting of an open posterior capsule. Intraoperative PCR management strategies should prioritize safety and strive to minimize vitreous traction, stabilize anterior chamber volume, maintain capsular and zonular integrity, and protect the corneal endothelium and other anterior segment structures. SUMMARY: With appropriate management of PCR and vitreous, surgeons may still deliver safe and satisfactory visual outcomes for modern cataract surgery.

Eyelid myeloid sarcoma: ominous presentation of acute myelogenous leukemia.

A 19 year-old African American man presented to our clinic for a second opinion about a right upper eyelid mass which had been recalcitrant to treatment for nonspecific orbital inflammation by an outside facility. Examination for systemic causes of the patients eyelid lesion led to a diagnosis of acute myelogenous leukemia (AML) FAB subtype M1. A subsequent biopsy of the eyelid tumor confirmed the diagnosis of a myeloid sarcoma. The patient succumbed to complications from his leukemia within 13 months of presentation. This case report is the first, to our knowledge, of an eyelid myeloid sarcoma as the presenting sign of AML and demonstrates the poor prognosis of this lesion.

Millimeter wave silicon micromachined waveguide probe as an aid for skin diagnosis--results of measurements on phantom material with varied water content.

BACKGROUND: More than 2 million cases of skin cancer are diagnosed annually in the United States, which makes it the most common form of cancer in that country. Early detection of cancer usually results in less extensive treatment and better outcome for the patient. Millimeter wave silicon micromachined waveguide probe is foreseen as an aid for skin diagnosis, which is currently based on visual inspection followed by biopsy, in cases where the macroscopical picture raises suspicion of malignancy. AIMS: Demonstration of the discrimination potential of tissues of different water content using a novel micromachined silicon waveguide probe. Secondarily, the silicon probe miniaturization till an inspection area of 600 × 200 µm2, representing a drastic reduction by 96.3% of the probing area, in comparison with a conventional WR-10 waveguide. The high planar resolution is required for histology and early-state skin-cancer detection. MATERIAL AND METHODS: To evaluate the probe three phantoms with different water contents, i.e. 50%, 75% and 95%, mimicking dielectric properties of human skin were characterized in the frequency range of 95-105 GHz. The complex permittivity values of the skin are obtained from the variation in frequency and amplitude of the reflection coefficient (S11), measured with a Vector Network Analyzer (VNA), by comparison with finite elements simulations of the measurement set-up, using the commercially available software, HFSS. The expected frequency variation is calculated with HFSS and is based on extrapolated complex permittivities, using one relaxation Debye model from permittivity measurements obtained using the Agilent probe. RESULTS: Millimeter wave reflection measurements were performed using the probe in the frequency range of 95-105 GHz with three phantoms materials and air. Intermediate measurement results are in good agreement with HFSS simulations, based on the extrapolated complex permittivity. The resonance frequency lowers, from the idle situation when it is probing air, respectively by 0.7, 1.2 and 4.26 GHz when a phantom material of 50%, 75% and 95% water content is measured. DISCUSSION: The results of the measurements in our laboratory set-up with three different phantoms indicate that the probe may be able to discriminate between normal and pathological skin tissue, improving the spatial resolution in histology and on skin measurements, due to the highly reduced area of probing. CONCLUSION: The probe has the potential to discriminate between normal and pathological skin tissue. Further, improved information, compared to the optical histological inspection can be obtained, i.e. the complex permittivity characterization is obtained with a high resolution, due to the highly reduced measurement area of the probe tip.

High-risk human papillomavirus-associated corneal/conjunctival intraepithelial neoplasia in a young patient.

Purpose: To report a case of high-risk human papillomavirus (HPV)-associated corneal/conjunctival intraepithelial neoplasia (CIN) in a 17-year-old fair-skinned male with no other risk factors. Observations: A 17-year-old Caucasian male presented with an 18-month history of left eye pain, redness, itchiness, and decreased vision. Examination revealed a leukoplakic nasal limbal/peripheral corneal lesion resistant to topical antibiotic and anti-inflammatory treatments. Excisional biopsy confirmed the diagnosis of CIN, and RNA in situ hybridization testing for high-risk HPV types 16/18 was positive. Subsequent testing of the patient for human immunodeficiency virus (HIV) returned negative. Conclusions and Importance: The median age of CIN diagnosis in the United States is in the sixth decade of life and is usually associated with a history of ultraviolet (UV) light exposure. There are reports of CIN in young patients with systemic immunodeficiency, immunosuppression, xeroderma pigmentosum, atopic dermatitis, asthma, and vaping. Here we present a case of high-risk HPV-associated CIN in a young, fair-skinned patient with no other identifiable risk factors.

Primary bulbar conjunctival basal cell carcinoma: A clinical-pathologic report and literature review.

Purpose: To enhance the characterization of primary bulbar conjunctival basal cell carcinoma (BCC) clinically and histologically, via report of a case and review of the relevant medical literature. Observations: We report the case of a 73-year-old man with no history of skin cancer who presented with a bulbar conjunctival nodule without connection to the eyelid or caruncle, originally thought to represent a pyogenic granuloma. After one month without improvement on topical prednisolone, excisional biopsy was performed, with routine histopathology and immunohistochemistry. The tumor was found histologically to be primary conjunctival BCC. Immunostaining exhibited negative Ber-EP4 and S100, mostly negative CK7 and EMA, and positive p63. Margins were negative, and the patient had no recurrence six months after excision. Conclusions and Importance: Primary conjunctival BCC must be considered in the differential diagnosis of a conjunctival lesion which may initially appear benign but does not behave as expected clinically. The location of the tumor in the case presented here refutes a prior postulate that primary conjunctival BCC arises from basal adnexal epithelium in the caruncle. Of the immunohistochemical findings, only the Ber-EP4 result differed from the typical immunostaining profile of cutaneous BCC. Further study is needed to determine the frequency of Ber-EP4 positivity in primary conjunctival BCC.

A randomized, open-label study of the tolerability and efficacy of one or three daily doses of ivermectin plus diethylcarbamazine and albendazole (IDA) versus one dose of ivermectin plus albendazole (IA) for treatment of onchocerciasis.

BACKGROUND: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. METHODS AND FINDINGS: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 µg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 µg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. CONCLUSIONS: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. TRIAL REGISTRATION: The study is registered at Cinicaltrials.gov under the number NCT04188301.

Human error and patient safety: interdisciplinary course.

BACKGROUND: The medical community has only recently begun to address how human error affects patient safety. In order to confront human error in medicine, there is a need to teach students who are entering the health professions how potential errors may manifest and train them to prevent or mitigate these problems. PURPOSE: The objective is to describe a semester-long, interdisciplinary, human error and patient safety course taught at the University of South Florida. METHODS: Six interdisciplinary groups, composed of students from five of the university's colleges, were formed. The curriculum consisted of expert lecturers, readings, case studies, and analysis of patient safety problems. Students were evaluated based on their group's work on the final project and peer evaluations. RESULTS: Nursing students scored the highest in each category evaluated. Physicians and medical students had the lowest evaluations in team participation and active engagement. All students rated the course highly and indicated that it enhanced their ability to work in interprofessional settings. CONCLUSIONS: The students showed improved knowledge and substantive skill level relative to patient safety and human error concepts. Working in interdisciplinary teams gave the students a better understanding of the role each discipline can have in improving health care systems and health care delivery.

A Reevaluation of the Tolerability and Effects of Single-Dose Ivermectin Treatment on Onchocerca volvulus Microfilariae in the Skin and Eyes in Eastern Ghana.

Mass administration of ivermectin (IVM) has significantly reduced onchocerciasis prevalence, intensity, and morbidity in most endemic areas. Most IVM clinical trials were performed long ago in persons with high-intensity infections that are uncommon in West Africa today. This cohort treatment study recruited participants from a hypoendemic area in eastern Ghana to reevaluate the efficacy and tolerability of IVM with a special focus on the kinetics of microfilaria (Mf) clearance. Mf in the skin and anterior chambers (AC) were assessed by skin snip and slit lamp examinations at baseline and at 3 and 6 months after treatment with IVM 150 µg/kg. Most participants (184-231, 79.7%) enrolled were treatment-naïve. The baseline geometric mean skin Mf count was 12.67/mg (range 3-86). Although persons with MfAC at baseline (64/231, 27%) had significantly higher skin Mf counts than people without MfAC, 7 of 39 (15%) of persons with skin Mf counts in the range of 3-5 Mf/mg had MfAC. Skin Mf were detected in 14% (31/218) and 45% (96/216) of participants 3 and 6 months after IVM treatment, respectively. MfAC were detected in 12 of 212 (5.7%) study participants at 6 months. 81% (187 of 231) of participants experienced 439 adverse events within 7 days after treatment; all adverse events were mild (96.1%) or moderate. This study has provided new data on the kinetics of Mf in the skin and eyes after IVM treatment of persons with light to moderate intensity Onchocerca volvulus infections that are common in Africa at this time.

Compositional Analysis of Extracellular Aggregates in the Eyes of Patients With Exfoliation Syndrome and Exfoliation Glaucoma.

Purpose: Exfoliation syndrome (XFS) is a condition characterized by the production of insoluble fibrillar aggregates (exfoliation material; XFM) in the eye and elsewhere. Many patients with XFS progress to exfoliation glaucoma (XFG), a significant cause of global blindness. We used quantitative mass spectrometry to analyze the composition of XFM in lens capsule specimens and in aqueous humor (AH) samples from patients with XFS, patients with XFG and unaffected individuals. Methods: Pieces of lens capsule and samples of AH were obtained with consent from patients undergoing cataract surgery. Tryptic digests of capsule or AH were analyzed by high-performance liquid chromatography-mass spectrometry and relative differences between samples were quantified using the tandem mass tag technique. The distribution of XFM on the capsular surface was visualized by SEM and super-resolution light microscopy. Results: A small set of proteins was consistently upregulated in capsule samples from patients with XFS and patients with XFG, including microfibril components fibrillin-1, latent transforming growth factor-ß-binding protein-2 and latent transforming growth factor-ß-binding protein-3. Lysyl oxidase-like 1, a cross-linking enzyme associated with XFS in genetic studies, was an abundant XFM constituent. Ligands of the transforming growth factor-ß superfamily were prominent, including LEFTY2, a protein best known for its role in establishing the embryonic body axis. Elevated levels of LEFTY2 were also detected in AH from patients with XFG, a finding confirmed subsequently by ELISA. Conclusions: This analysis verified the presence of suspected XFM proteins and identified novel components. Quantitative comparisons between patient samples revealed a consistent XFM proteome characterized by strong expression of fibrillin-1, lysyl oxidase-like-1, and LEFTY2. Elevated levels of LEFTY2 in the AH of patients with XFG may serve as a biomarker for the disease.

Dense Deposit Disease Involving C3 and C4d Deposits.

Dense deposit disease (DDD), earlier called Type II membranoproliferative glomerulonephritis is distinct disease having frequent relapses reaching end-stage kidney disease by 10-year in up to 50%-60% of cases and high recurrence rate in the allograft. The term DDD is derived from its distinctive ribbon-like osmiophilic deposits in the lamina densa of glomerular basement membrane by electron microscopy. Pathogenetically, alternate pathway dysfunction leads to this disease, which is diagnosed by ultrastructure. Herein, we describe our observation of C4d positivity in an adolescent boy with DDD.

Reproductive Regulation of Gene Expression in the Hypothalamic Supraoptic and Paraventricular Nuclei.

Oxytocin secretion is required for successful reproduction. Oxytocin is synthesised by magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei and the physiological demand for oxytocin synthesis and secretion is increased for birth and lactation. Therefore, we used a polymerase chain reaction (PCR) array screen to determine whether genes that might be important for synthesis and/or secretion of oxytocin are up- or down-regulated in the supraoptic and paraventricular nuclei of late-pregnant and lactating rats, compared to virgin rats. We then validated the genes that were most highly regulated using real time-quantitative PCR. Among the most highly regulated genes were those that encode for suppressors of cytokine signalling, which are intracellular inhibitors of prolactin signalling. Prolactin receptor activation changes gene expression via phosphorylation of signal transducer and activator of transcription 5 (STAT5). Using double-label immunohistochemistry, we found that phosphorylated STAT5 was expressed in almost all oxytocin neurones of late-pregnant and lactating rats but was almost absent from oxytocin neurones of virgin rats. We conclude that increased prolactin activation of oxytocin neurones might contribute to the changes in gene expression by oxytocin neurones required for normal birth and lactation.

Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions.

PURPOSE: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. METHODS: Case series. RESULTS: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. CONCLUSIONS: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration.

Use of Topical Besifloxacin in the Treatment of Mycobacterium chelonae Ocular Surface Infections.

PURPOSE: To present the clinical outcome of 3 cases of ocular surface infections by Mycobacterium chelonae treated with besifloxacin (0.6%, Besivance; Bausch & Lomb, Tampa, FL). METHODS: In this retrospective review of a small case series, we reviewed the medical records of 3 clinical patients with M. chelonae infection involving the ocular surface. Besifloxacin was used as an adjunct in 2 cases of keratitis and as the principal therapeutic agent in a case of nodular conjunctivitis. RESULTS: Two patients who presented with culture-proven M. chelonae keratitis initially had been treated with topical amikacin and oral clarithromycin for 6 months in the first case and for 2 months in the second without complete resolution. Topical besifloxacin was added as an adjunct therapy to amikacin with progressive weaning of clarithromycin. Both cases of keratitis eventually resolved without recurrence after discontinuation of topical amikacin and besifloxacin. A third patient presented with nodular conjunctival inflammation, which initially had been treated with topical ciprofloxacin and corticosteroids without improvement. One nodular lesion was excised and submitted for microbial culture, which revealed the growth of M. chelonae. Marked improvement of the conjunctivitis was noted after 3 weeks of treatment with topical besifloxacin. Complete resolution of the conjunctival nodules was achieved after 10 weeks of treatment with besifloxacin. CONCLUSIONS: Topical besifloxacin seems to be a useful adjunct agent in the treatment of nontuberculous mycobacterial keratitis by M. chelonae and may be viable for use as a first-line agent in cases of nodular conjunctivitis by M. chelonae.

Quantitation of prolactin receptor mRNA in the maternal rat brain during pregnancy and lactation.

Prolactin receptor (PRL-R) expression in the brain is increased in lactating rats compared with non-pregnant animals. The aim of the present study was to determine the time-course of changes in PRL-R mRNA levels during pregnancy and/or lactation, and to determine relative levels of the two forms (short and/or long form) of receptor mRNA in specific brain regions. Brains were collected from female rats on dioestrus, days 7, 14 or 21 of pregnancy, day 7 of lactation or day 7 post-weaning. Frozen, coronal sections were cut (300 microm) and specific hypothalamic nuclei and the choroid plexus were microdissected using a punch technique. Total RNA was extracted and reverse transcribed, then first strand cDNA was amplified using quantitative real-time PCR. Results showed an up-regulation of long-form PRL-R mRNA in the choroid plexus by day 7 of pregnancy compared with dioestrus, which further increased on days 14 and 21 of pregnancy and day 7 of lactation, and then decreased to dioestrous levels on day 7 post-weaning. Short-form PRL-R mRNA levels increased on day 14 of pregnancy relative to dioestrus, increased further on day 7 of lactation and decreased on day 7 post-weaning. Changes in mRNA were reflected in increased levels of PRL-R immunoreactivity in the choroid plexus during pregnancy and lactation, compared with dioestrus. In the arcuate nucleus, long-form PRL-R mRNA was increased during pregnancy. In contrast to earlier work, no significant changes in short- or long-form PRL-R mRNA expression were detected in several other hypothalamic nuclei, suggesting that changes in hypothalamic mRNA levels may not be as marked as previously thought. The up-regulation of PRL-R mRNA and protein expression in the choroid plexus during pregnancy and lactation suggest a possible mechanism whereby increasing levels of peripheral prolactin during pregnancy may have access to the central nervous system. Together with expression of long-form PRL-R mRNA in specific hypothalamic nuclei, these results support a role for prolactin in regulating neuroendocrine and behavioural adaptations in the maternal brain.

Timentin therapy for bone, joint, and deep soft tissue infections in children.

Timentin, a combination of clavulanic acid (0.1 g) and ticarcillin (3.0 g), has proved effective in vitro against bacterial pathogens that produce beta-lactamases. The usual etiologic bacteria of osteochondritis of the foot (Pseudomonas species) and osteomyelitis/septic arthritis (Staphylococcus aureus) are commonly resistant to penicillins. To date, we have used Timentin to treat 30 children with bone, joint, and deep soft tissue infections. Timentin was administered intravenously at an average dosage of 207 mg/kg per day for mild to moderate infection and 310 mg/kg per day for bone and joint infections with systemic signs (sepsis). The lower dose was used in 24 patients and the other six patients, who had signs of sepsis, received the higher dose. All patients received Timentin intravenously over 30 minutes every four to six hours for a minimum of five days (mean 6.6 +/- 2.6 days, range five to 14 days). The mean time to defervescence and/or reduction in clinical symptoms was 1.6 +/- 1.3 days (range zero to four days). Osteochondritis due to P. aeruginosa was diagnosed in six patients, and septic bursitis, osteomyelitis, or septic arthritis due to S. aureus (13 patients) or Staphylococcus species and group A streptococci (four patients) was diagnosed in 17 patients. All isolates were susceptible to Timentin in vitro by disk-diffusion analysis. All patients showed a response to therapy with Timentin, with or without surgical intervention. All patients had clinical and microbiologic cures; no adverse reactions or side effects were observed. There have been no clinical or microbiologic relapses to date. Timentin may prove to be useful in specific bone and joint infections in children.

Effect of nitroglycerin ointment on the clinical and hemodynamic response to exercise.

The effects of nitroglycerin ointment (15 mg nitroglycerin) on hemodynamics at rest and during exercise were studied in 12 patients with coronary artery disease and exertional angina (angina group) and in 8 patients with normal coronary arteriograms or with nonsignificant arteriographic abnormalities who did not have exertional chest pain (nonangina group). In both groups at rest nitroglycerin ointment induced within 15 minutes a significant decrease in left ventricular end-diastolic pressure that was sustained for at least 60 minutes; systemic arterial pressure also decreased within 15 minutes and continued to decrease during the 60 minutes of observation. By 30 to 60 minutes there were significant decreases in cardiac index, stroke index, left ventricular stroke work index and tension-time index. During exercise performed 60 minutes after receiving nitroglycerin ointment, 10 of the 12 patients in the angina group had no pain, whereas 2 had delayed and less severe symptoms. Hemodynamic observations during this exercise period revealed significant decreases in left ventricular end-diastolic pressure, systemic pressure and tension-time index from values in the initial exercise period; heart rate remained unchanged. These data document the protective effect of nitroglycerin ointment for a period of at least 60 minutes and also suggest that the beneficial effects are related to a reduction in myocardial oxygen requirements.