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Background: Coronary artery bypass grafting (CABG) remains a cornerstone in the management of coronary artery disease (CAD). In nonurgent surgical revascularization cases, preoperative optimization of modifiable risk factors can improve outcomes. There is increasing interest in the relationship between lipoprotein(a) levels and the risk for ischemic cardiovascular disease, particularly how CABG outcomes are in turn affected. This review highlights the role of lipoprotein(a) in the pathogenesis of CAD and CABG outcomes and discusses future directions for its optimal management in the perioperative period., Methods: The PubMed/MEDLINE database was reviewed until March 2024 to capture publications that evaluated and/or described the relationship between lipoprotein(a) and CABG surgery or CAD outcomes., Results: The available literature supports lipoprotein(a) as a causal and independent risk factor for the pathogenesis of CAD. Elevated lipoprotein(a) levels are associated with an increased risk of adverse post-CABG outcomes, including graft occlusion incidence and major adverse cardiovascular events. Genetic variations influencing lipoprotein(a) levels play a role in disease progression and surgical outcomes. Several therapies aimed at reducing lipoprotein(a) levels, currently in phase III clinical trials, show promise for improving the prognosis after CABG., Conclusions: Among individuals undergoing surgical revascularization for CAD, lipoprotein(a) levels may help define risk and inform best practices for perioperative management. We advocate for the routine measurement of lipoprotein(a) in all patients undergoing CABG. Emerging lipoprotein(a)-lowering agents show promise for secondary prevention of cardiac events, although dedicated analyses in cardiac surgical subcohorts will be important to evaluate their role in improving CABG outcomes., Competing Interests: Disclosures Nitish K. Dhingra reports nonfinancial support from Amarin, Boehringer Ingelheim, Eli Lilly, Lexicon Pharmaceuticals, and Sanofi. Tayyab S. Khan has received honoraria from Abbott, Amgen, AstraZeneca, Bausch, Boehringer Ingelheim, the Canadian Medical and Surgical Knowledge Translation Research Group, the CPD Network Association, Eli Lily Canada, Janssen, Novo Nordisk Canada, and Sutherland Global Services Canada ULC, and has served on advisory boards for Amgen, Apotex, Eli Lily Canada, and Novo Nordisk. David A. Hess is the Sheldon H. Weinstein Chair in Diabetes Research at the Schulich School of Medicine, Western University. Marlys L. Koschinsky has received grant support and/or speaking/lecture fees from Amgen, Eli Lilly, Novartis, and Regeneron. Hwee Teoh has received personal fees from the Canadian Medical and Surgical Knowledge Translation Research Group. Subodh Verma holds a Tier 1 Canada Research Chair in Cardiovascular Surgery and reports receiving grants and/or research support and/or speaking honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Humber River Health, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, S & L Solutions Event Management Inc, Sanofi, and Sun Pharmaceuticals. The other authors have no conflicts of interest to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: A new method for assessing female sexual arousal through changes in slow oscillatory patterns in vaginal blood flow was first described in the previous manuscript [1]. This method was translational and discriminated between normal healthy volunteers and women with female sexual arousal disorder., Aim: These studies addressed the influence of autonomic and central nervous systems on slow vaginal blood flow oscillations in rats., Methods: Vaginal blood flow oscillations were measured in urethane-anesthetized rodents using laser Doppler flowmetry. Acquired data were filtered for frequency analysis range of 0.013-2.5 Hz., Main Outcome Measures: Data were assessed for changes in a high frequency range (HF = 0.6-2.5 Hz), and low frequency range (LF = 0.013-0.6 Hz)., Results: The basal HF oscillatory component of vaginal blood flow was primarily vagally mediated, although could be modulated pharmacologically with p-chloroamphetamine in the absence of vagal innervation. The LF component could be modulated by antagonists of noradrenergic receptors but did not appear to be dependent upon tonic activation of sympathetic circuitry. The non-selective dopamine receptor agonist apomorphine induced changes in vaginal blood flow oscillations consistent with sexual arousal during metestrus in the presence of the peripheral antagonist domperidone but not in the presence of the centrally acting antagonist haloperidol. Electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus induced an anti-arousal response in vaginal blood flow oscillations. These data demonstrated that manipulation of the central nervous system alone (via centrally acting apomorphine or electrical stimulation of the PVN) could produce either a pro-arousal or an anti-arousal response in vaginal blood flow oscillations. Alterations in the LF/HF ratio measured from vaginal laser Doppler flowmetry were independently regulated from vasculature in the trunk, the tongue, and electrocardiogram-derived heart rate variability, and were independent of overall vasocongestion of the vagina as measured by mean blood flow., Conclusions: These data indicated that slow oscillations in vaginal blood flow from rodents may be utilized as an animal model of female sexual arousal. Changes in these oscillations are driven by the central nervous system and modulated by the autonomic nervous system.

Purpose: This study investigated slow oscillatory rhythms in vaginal blood flow as a physiological marker of female sexual arousal in rodents, human healthy volunteers, and women with female sexual arousal disorder (FSAD)., Materials and Methods: Vaginal blood flow was measured in urethane-anesthetized rodents using laser Doppler flowmetry, while in humans, vaginal photoplethysmography was used. Acquired data were filtered for frequency analysis in the range of 0.013-2.5 Hz in rodents and 0.01-0.5 Hz in humans. Rodents were assessed for changes in a high frequency range (HF = 0.6-2.5 Hz), and a low frequency range (LF = 0.013-0.6 Hz). Human data were assessed for total spectral power in the entire frequency range., Results: During naturally induced arousal (exposure to male), oscillatory rhythms in vaginal blood flow from rodents demonstrated an increase in the ratio of LF oscillations to HF oscillations (LF/HF ratio). Drugs known to induce sexual arousal (apomorphine and melanotan II) were tested in anesthetized rodents. Both compounds induced an increase in the LF/HF ratio. In humans, visual sexual stimulation induced an increase in the total power of slow oscillatory activity in vaginal blood flow in healthy human volunteers. No such increase was observed in women with FSAD., Conclusions: This study demonstrated that slow oscillations in vaginal blood flow are correlated with subjective physiological arousal and display diminished responsiveness in women with FSAD. Slow oscillations in vaginal blood flow are entirely independent of vaginal vasocongestion as women with FSAD demonstrated a normal vasocongestion response to visual sexual stimulation. In conditions where rodents would be expected to be sexually aroused, slow oscillations in vaginal blood flow showed a shift from HFs to LFs. This technique will greatly enhance the investigation of female sexual function both clinically and preclinically.

There are several conditions associated with dysfunction of the lower urinary tract or which result in a reduction in the ability to engage in satisfactory sexual function and result in significant bother to sufferers, partners and/or carers. This review describes some of the animal models that may be used to discover safe and effective medicines with which to treat them. While alpha adrenoceptor antagonists and 5-alpha-reductase inhibitors deliver improvement in symptom relief in benign prostatic hyperplasia sufferers, the availability of efficacious and well-tolerated medicines to treat incontinence is less well served. Stress urinary incontinence (SUI) has no approved medical therapy in the United States and overactive bladder (OAB) therapy is limited to treatment with muscarinic antagonists (anti-muscarinics). SUI and OAB are characterised by high prevalence, a growing ageing population and a strong desire from sufferers and physicians for more effective treatment options. High patient numbers with low presentation rates characterizes sexual dysfunction in men and women. The introduction of Viagra in 1998 for treating male erectile dysfunction and the success of the phosphodiesterase type 5 inhibitor class (PDE5 inhibitor) have indicated the willingness of sufferers to seek treatment when an effective alternative to injections and devices is available. The main value of preclinical models in discovering new medicines is to predict clinical outcomes. This translation can be established relatively easily in areas of medicine where there are a large number of drugs with different underlying pharmacological mechanisms in clinical usage. However, apart from, for example, the use of PDE5 inhibitors to treat male erectile dysfunction and the use of anti-muscarinics to treat OAB, this clinical information is limited. Therefore, current confidence in existing preclinical models is based on our understanding of the biochemical, physiological, pathophysiological and psychological mechanisms underlying the conditions in humans and how they are reflected in preclinical models. Confidence in both the models used and the pharmacological data generated is reinforced if different models of related aspects of the same disorder generate confirmatory data. However, these models will only be fully validated in retrospect once the pharmacological agents they have helped identify are tested in humans.

Purpose: To evaluate the safety and efficacy of surgical implantation of prosthetic iris devices in patients with iris deficiency., Methods: Nine patients with traumatic iris defects, congenital aniridia or iris coloboma, and surgical or optical iridectomies were included in a noncomparative case series. Cataract surgery with intraocular lens and prosthetic iris implantation was performed in 10 eyes. The visual acuity, subjective degree of glare disability, postoperative anatomic results, and intraoperative and postoperative complications were evaluated., Results: The mean follow-up was 17.75 months (range 4-48 months). Best-corrected visual acuity improved in nine of 10 eyes (90%) and remained unchanged in one eye. Glare subjectively improved in four of five eyes (80%) of patients complaining of glare preoperatively. All eyes achieved the desired anatomic result. Intraoperative complications included one anterior capsular tear. Postoperative complications included a short period of mild postoperative anterior uveitis in four eyes. Secondary glaucoma was absent., Conclusion: In patients with iris deficiency, implantation of prosthetic iris device, and intraocular lens implant following cataract surgery appears to be safe and effective in reducing glare disability and improving visual outcomes.

Objective: To document adverse effects of anabolic-androgenic steroid (AAS) use in community-based users attending a medical clinic., Design and Setting: Prospective recruitment, questionnaire-based interview, physical examination and investigations, with follow-up, of people who attended, anonymously, an inner-city hospital clinic established specifically to examine AAS use., Participants: 58 men, comprising 27 past AAS users, 14 present users and 17 potential users (who formed the control group)., Main Outcome Measure: Clinical adverse effects and abnormal laboratory findings., Results: Cyclical use of oral and intramuscular, human and veterinary AASs were reported. The most commonly reported source of AASs was friends (59%), gymnasiums (25%) and doctors (14%). The most common reported adverse effects were alterations in libido (61%), changes in mood (48%), reduced testis volume (46%) and acne (43%). Although mean systolic and diastolic blood pressure was not significantly different between groups, five present (29%), 10 past (37%) and one potential user (8%) were hypertensive. Gynaecomastia was found in 10 past users (37%; P<0.01 v. potential users), two present users (12%) and no potential users. Mean testis volume was significantly smaller in present users (18 mL; P<0.02) than in the other groups. Twenty past users (83%), eight present users (62%) and five potential users (71%) had abnormal liver function test results (P=0.5). After discussion of test results, only 11 participants (19%) reported they would not use AASs in the future., Conclusions: Adverse effects were reported by or detected in most of the AAS users who attended the clinic. Despite awareness of adverse consequences, most participants planned future use of AASs.

Spontaneous pneumomediastinum is a rare complication of diabetic ketoacidosis. We report two patients with this complication who presented to a Sydney hospital within one week. Although both patients were young backpackers, staying at the same hostel, we believe this was coincidental.

RP 64477 (N-butyl-3-(p-decyloxybenzamido)-4-(methylthio)benzamide) has been shown to be a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (EC 2.3.1.26; ACAT) in intestinal, hepatic, adrenal, and arterial tissue preparations obtained from a range of animal species. Drug concentrations producing 50% inhibition of enzyme activity (IC50 values) ranged from 14-283 nM. Inhibition by RP 64477 in a rabbit intestinal enzyme preparation was shown to be non-competitive with respect to the substrate oleoyl-CoA. In whole cell assays using human intestinal (CaCo-2), hepatic HepG2) and monocytic (THP-1) cell lines, RP 64477 inhibited ACAT activity with IC50s of 113, 503, and 180 nM, respectively. RP 64477 (0.03% w/w by diet) reduced significantly cholesterol absorption in cholesterol/cholic acid-fed rats from 94+/- 8% to 65 +/- 4%. In cholesterol-fed rabbits, cholesterol absorption was reduced from 72 +/- 5% to 50 +/-5% and 44 +/- 5% at dose levels of 10 and 30 mg kg-1 b.i.d., respectively. Plasma cholesterol levels were reduced dose-dependently in both cholesterol/cholic-acid-fed rats and cholesterol-fed rabbits. Neither cholesterol absorption nor plasma cholesterol levels were reduced significantly in animals maintained on standard laboratory diets. Pharmacokinetic studies indicated that RP 64477 were very poorly absorbed following oral administration to rats. Plasma levels of drug were < 2 ng mL-1 following a dose of 2000 mg kg-1 p.o.. When radiolabelled RP 64477 was administered orally, limited absorption was indicated by the overwhelming elimination of radioactivity in the faces (96.4% of administered material) coupled with low renal clearance (0.6% of dose) and biliary excretion (0.05% of dose). In conclusion, this work shows that RP 64477 is a potent inhibitor of ACAT obtained from a range of animal species and man. Inhibition of cholesterol absorption and hypocholesterolaemic activity has been demonstrated in rats and rabbits maintained on diets supplemented with cholesterol. Pharmacokinetic studies indicate low systemic exposure to RP 64477 as a result of limited absorption of this drug.

Interleukin-1 beta (IL-1 beta) may be related to the pathological processes associated with periodontitis, primarily due to its ability to induce collagenase, increase neutrophil chemotaxis, and stimulate bone resorption. This study was designed to histologically quantitate IL-1 beta positive cells from various histologic fields in untreated gingivitis/early periodontitis (G/EP) versus moderate/severe periodontitis (M/SP) gingival tissues, and associate these with collagen loss. Two gingival biopsies from 8 patients were collected, one from a G/EP site and one from a M/SP site. Mouse monoclonal antibodies in combination with an avidin-biotin-peroxidase system were used to stain for IL-1 beta, while the van Gieson method was used to stain for collagen in serial sections. Collagen loss in G/EP (35%) and M/SP (52%) fields was consistent with gingivitis and periodontitis, respectively. IL-1 beta positive cells in combined coronal/sulcular (Co/Su) and apical/sulcular (Ap/Su) fields (nearest the bacterial insult) were significantly more numerous compared to combined coronal/middle (Co/Mi) and apical/middle (Ap/Mi) fields (p < 0.05). While numbers and percentages of IL-1 beta positive cells were generally higher in M/SP biopsies, differences were not significant. Further, there was no correlation between the number of IL-1 beta positive cells and percent collagen loss. However, a significant correlation between IL-1 beta positive cells and corresponding gingival crevicular fluid IL-1 beta concentrations was noted (r = 0.65, p = 0.01). Through the use of immunohistochemistry, this study demonstrated that the presence of IL-1 beta + cells does not appear to have a direct association with collagen loss.

A review if presented of the use of low-dose insulin infusion in the management of 58 episodes of severe diabetic hyperglycaemia. Neutral insulin in a dosage of 2-4 units per hour is infused via a paediatric giving set to achieve a sustained physiological elevation of insulin levels. This method is safe, simple and rapidly effective in lowering the blood glucose level, the mean rate of fall (62 mg/100 ml/hr, or 11% per hour) being unaffected by prior insulin therapy, acidosis or ketonuria. Classification of the hyperglycaemia as ketoacidotic or hyperosmolar is unnecessary before insulin therapy is instituted, as the relative decline in glucose level is the same in the hyperosmolar non-ketotic group as in the others. Proven infection significantly lowers the rate of fall of glucose level. Hypoglycaemia and hypokalaemia are rare during low-dose infusion. Early and adequate replacement with potassium phosphate is recommended, oral potassium supplements being continued for several days. Bicarbonate therapy is rarely indicated in the management of acidosis. No patient had cerebral oedema during treatment, and one elderly patient with extensive pneumonia and empyema died during the infusion. It is suggested that continuation of low-dose insulin infusion, together with 5% dextrose solution, after the plasma glucose level reaches 200 mg/100 ml, may hasten the clearance of ketones, preventing relapse.

Twenty-five women with hirsutism were studied before and during treatment aimed empirically at suppresing testosterone production by adrenals, ovaries or both. Mean basal plasma testosterone was 70 plus or minus 30 ng/dl, significantly (P less than 0.01) higher than the mean of twenty-three normal women; basal metabolic clearance rate (MCR) of testosterone was also higher (P less than 0.01) than that reported for normal women. Production rate (PR) of testosterone exceeded 417 mug/24 h (1 SD above the mean reported for normal women), in nineteen of the twenty-five patients. After 4 months, small dose betamethasone therapy (0.5 mg at bed time) had reduced the mean PR of testosterone in thirteen patients from 509 mug/24 h to 356 mug/24 h (P = 0.05); anovulatory steroids reduced mean PR of testosterone in nine from 612 mug/24 h to 345 mug/24 h (P less than 0.05, greater than 0.025), and the combination of both therapies in ten reduced PR of testosterone from 528 mug/24 h to 148 mug/24 h (P less than 0.001). The latter regimen had moderate success in reducing hair growth (in six out of ten). Fourteen of the twenty-five claimed benefit in hirsutism and all thirteen with acne were improved. In individual cases, clinical benefit did not correlate well with reduction in PR of testosterone. Freedom from undesirable side effects allows these well-accepted forms of treatment to be given even longer trials.

Efforts to understand and prevent pontine and extrapontine myelinolysis have focused on the correction of hyponatremia, but controversy persists. We report a woman who presented in hyperosmolar diabetic coma with hypernatremia (169 mEq/l) and hyperglycemia (954 mg/dl). Plasma sodium rapidly increased to 188 mEq/l before gradually returning to normal. She remained obtunded and died 21 days later. Autopsy showed widespread, symmetrical demyelination involving the subcortical white matter, corpus callosum, anterior commissure, extreme, external, and internal capsules, fornix, thalamus, cerebellum, and lateral pons. The central pons and lateral geniculate nuclei were uninvolved. This case illustrates that lateral pontine and extrapontine myelinolysis can be associated with hypernatremia and hyperosmolality. In both hypo- and hypernatremic states, the significant event may be an increase in serum sodium or serum osmolality of sufficient rapidity and magnitude.

When hirsutism is recognised as an endocrinopathy, a rational approach to treatment can be devised. In simple hirsutism, the ovaries are the most likely source of excess androgen production, and demonstrate a wide range of pathology. The adrenal cortex is sometimes of prime importance but is more frequently a contributor of androgen precursors. Long term hormonal suppressive treatment will successfully control hirsutism in the majority. Antiandrogens constitute a potential treatment for future years; physical methods of depilation remain as useful adjuncts to medical therapy.

Castleman's disease is a rare, benign lymphoproliferative disorder that usually arises in lymph nodes, most commonly in the mediastinum. The authors report the clinical and pathological features of three patients with localized Castleman's disease of the leptomeninges. There were two women, aged 63 and 82 years, and one 25-year-old man. Two patients had progressive focal motor seizures of 3 and 24 months' duration, and the third patient presented acutely with generalized seizures. The clinical diagnosis was meningioma in each case, based on computerized tomography scans, cerebral arteriography, and the operative findings. All three lesions arose in the leptomeninges, compressed the underlying cerebral cortex, and infiltrated the overlying dura to a variable extent. Surgical excision of the tumor resulted in marked clinical improvement in all three patients. Histologically, two cases were classified as the hyaline-vascular type and one as the plasma cell type. Immunohistochemical stains of the latter case revealed a monoclonal population of mature plasma cells. Only a few scattered polyclonal plasma cells were seen in the other two cases. The authors conclude that Castleman's disease involving the leptomeninges is a rare disorder that may mimic meningioma clinically and radiographically.

Remission induction therapy with 6MP and adriamycin in combination was administered to 19 adult leukemic patients refractory to previous therapy. Eight patients also received vincristine and prednisone. Thirteen patients had acute myelogenous leukemia, 3 undifferentiated leukemia, and 3 blastic transformation of chronic myelogenous leukemia. Four patients achieved remission but in only 2 were the remissions complete. Eleven patients failed to respond. Ten of the 19 patients developed unexpected severe liver toxicity manifested by a clinical picture of cholestasis (in the majority) or ascending cholangitis (in 2 patients). In the postmortem examination of 8 patients there was cholestasis and mild to severe hepatocellular damage in all.

Fine-needle aspiration cytology of the prostate is becoming increasingly accepted and used in the United States. This is a report of the experience of a nonacademic practice in which the aspirations were performed by a number of urologists, usually in the office, and were interpreted by a number of pathologists with varying degrees of experience in cytopathology. Of 187 patients, 159 had smears adequate for evaluation, and 99 had histologic/substantiating clinical follow-up for comparison. The resulting specificity was 97%, sensitivity was 91%, and the false-negative rate was 9%. These figures compare favorably with those reported in studies from academic university-based practices.

Women commonly complain of excess facial or body hair. There are generally no other abnormal physical findings and the relevance of other symptoms, especially those related to the menstrual cycle, may be unclear. The theme of androgen excess provides an explanation for the sign and various symptoms, and suggests certain pathology. Rational therapy can be based on and understanding of the hormonal processes involved in the development of secondary sexual hair. Treatment of simple hirsutism is well tolerated even in prolonged courses, and in most cases produces a satisfactory cosmetric result.

A technique has been developed in which progesterone may be measured by radioimmunoassay in unextracted serum. The method depends on the displacement of progesterone from serum binding proteins by danazol, [17 alpha-pregn-4-en-20-yno (2,3-d) isoxazol-17-ol], a compound which also blocks recombination of free progesterone with proteins and does not cross react with the progesterone antiserum. This new method saves time and labour, and fulfills the criteria of sensitivity and precision for clinical use. The results correlate well with those of conventional assays for progesterone.

Eleven adults with refractory leukemia treated with a combination of 6-mercaptopurine and Adriamycin developed hepatic dysfunction manifested by elevations of serum total bilirubin, alkaline phosphatase, and glutamic oxaloacetic transaminase. Liver tissue obtained at necropsy showed intrahepatic cholestasis (eight cases), hepatocellular necrosis (ten cases), leukemic infiltration (two cases), and fatty change (nine cases). Neither this frequency nor severity of hepatocellular destruction has hitherto been associated with 6-mercaptopurine at the dose levels used in this study, nor has Adriamycin previously been found to be hepatotoxic. It is postulated that Adriamycin potentiated the hepatotoxicity of 6-mercaptopurine in these patients.

Twenty-four karotypically proven patients with Klinefelter's syndrome were studied. The majority suffered from disorders of personality and social adjustment. All were poorly educated. Two-thirds showed gynaecomastia and all had small testes. Eunuchoid body proportions were seen in the majority of patients. Half the patients had plasma androgen levels in the low normal range; in the rest the levels were subnormal. The serum LH level was elevated in 80% and could not be adequately suppressed by exogenous androgens in seven out of nine patients. Abnormalities of carbohydrate metabolism were demonstrated in seven patients. Bilateral mastectomy was a valuable form of therapy, but androgens were withheld for phychosocial reasons.

The experience of 31 patients with primary adrenal tumours seen in one teaching hospital over a 10-year period is reviewed. There were 10 patients who had benign cortical adenomas; 11 had adrenal cortical carcinomas, and 10 had phaeochromocytomas, one of which was malignant. During the review period, a primary adrenal mass was discovered in 5% of 2951 autopsies performed in the study institution. The diagnosis and management of these uncommon tumours is reviewed.

Two women with primary amenorrhoea and few other stigmata of Turner's syndrome were found to be chromosome mosaics: 45,X/46,X,idic(Y). In Case 1, the dicentric isochromosome Y was found to have a long-arm breakpoint of formation. This structure was interpreted as containing two Y short arms and centromeres separated by a region derived from the proximal Y long arm. One of the centromeres in the Case 1--idic(Y) was suppressed in 80% of cells in blood, and in these cells it appeared as a regular Y-shaped chromosome. In Case 2 the idic(Y) was derived by a short-arm breakpoint of formation. In all the dicentrics of this case with one primary constriction (functional monocentrics) there was a single Cd band. In the 10% of dicentrics with two primary constrictions, there were two Cd bands. It is argued that the instability of sex isochromosomes is due to this functional dicentricity in some cells. These cases are compared with 42 other Y isochromosomes with various short- and long-arm breakpoints of formation. It is suggested that some of the nonheterochromatic, nonfluorescent Y chromosomes previously reported may be explained as dicentric i(Y) with proximal long-arm breakpoints of formation and one suppressed centromere.