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The effects of 6 weeks of thrice weekly training on glycaemic control were assessed in 20 sedentary Type 2 (non-insulin-dependent) diabetic patients and 11 control subjects matched for previous physical activity. Maximal oxygen uptake was lower in the diabetic patients than in control subjects before training (26.2±1.1 versus 32.6±1.7 ml·kg·min; p<0.001). Glycosylated haemoglobin levels decreased in the diabetic patients during the training programme (12.2±0.5 to 10.7±0.4%; p < 0.02). Oral and intravenous glucose tolerance determined 72 h after the last exercise period showed only minimal improvement. Plasma glucose levels were, however, significantly lower at 12 h than 72 h after exercise in eight subjects tested at both time points. These data suggest that an exercise programme can produce a significant decrease in glycosylated haemoglobin levels in Type 2 diabetic males probably due, in great measure, to the cumulative effect of transient improvements in glucose tolerance which follow each individual period of exercise. [ABSTRACT FROM AUTHOR]

A total of 74 hypercholesterolemic patients were randomized to receive double-blind treatment for 6 weeks with either 20 mg of fluvastatin daily or placebo. Open-label niacin, to a maximum of 3 g daily, was added to each treatment for a further 9 weeks. Changes in lipid parameters were derived from averaged data, with monotherapy at weeks 3 and 6 and with combination therapy at weeks 12 and 15. The reduction in low-density lipoprotein cholesterol (LDL-C) was significantly greater with fluvastatin (20.8%) compared with placebo (p < 0.001) after 3-6 weeks of treatment. At the end of 12-15 weeks, the addition of niacin potentiated the response to 43.7% with the fluvastatin+niacin combination and to 26.5% with the placebo+niacin combination (p < 0.001, vs baseline and between treatment groups). Significant gender differences were noted in the LDL-C response to the fluvastatin+niacin combination. Women achieved LDL-C reductions of 54.6% whereas men achieved reductions of 38.2% (p < 0.0005, between gender groups). Women also tended to have greater LDL-C reductions with the placebo+niacin combination, compared with men (p < 0.05). At the end of 12-15 weeks, there were HDL-C increases of 33.1% (p < 0.001) whereas triglyceride levels declined by 32.3% (p < 0.001). In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective and well-tolerated alternative for the treatment of hypercholesterolemia. The differential response in LDL-C between men and women should be further explored in other trials of lipid-lowering therapy. [ABSTRACT FROM AUTHOR]

PRAME (PReferentially expressed Antigen in MElanoma), a cancer-testis antigen expressed in normal and neoplastic tissues with several functions, proved to be a useful diagnostic tool in the differential diagnosis between benign and malignant melanocytic lesions. The current study aims to perform PRAME stain on a retrospective case series of mucosal melanocytic tumors of the head and neck region to compare 3 different scores and evaluate the most reliable one in this diagnostic set. Immunohistochemical analysis for PRAME was performed in 54 benign and malignant mucosal melanocytic tumors of the head and neck region collected from 41 patients. The best-performing cutoff of PRAME-positive cells (nuclear stain) to differentiate benign and malignant mucosal melanocytic tumors of the head and neck region is that proposed by Raghavan and colleagues (<60%/≥60% of PRAME-positive cells), with 100% and 77.8% of benign lesions and malignant tumors respectively correctly identified. Applying this score, PRAME stain showed the best results (sensitivity, specificity, accuracy, and positive and negative predictive values) for the diagnosis of head and neck melanocytic tumors. However, a subset of PRAME-negative malignant tumors was identified, especially located in the palatal area (hard and soft palate). Finally, high PRAME expression (≥60%) was associated with specific sites (nasal cavity/nasal septum/turbinates nasopharynx, and the maxillary sinus), nodular histotype, and female sex., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Non allergic rhinitis (NAR) comprises different clinical definitions and phenotypes, including non inflammatory non allergic (NINAR) and cellular inflammatory forms. Nasal cytology, usually performed by scraping the inferior turbinate, is a non invasive, cheap and point-of-care tool to distinguish among the different NAR phenotypes, but still a relevant proportion of patients evaluated by nasal cytology receive a non precise definition of NAR phenotype. We hypothesize that collecting nasal cytology samples from middle meatus could increase the diagnostic accuracy., Methods: Consecutive patients with chronic rhinitis without evidence of allergic sensitization were assessed for nasal cytology by means of scraping both the inferior turbinate and the middle meatus (lateral-inferior wall of the middle turbinate)., Results: 107 consecutive patients with NAR were enrolled in the study. According to inferior turbinate cytology, 42.1% were defined as affected by NINAR, 2.8% by bacterial rhinitis, 10.3% by non allergic rhinitis with eosinophils (NARES), 15.0% non allergic rhinitis with neutrophils (NARNE), 19.6% non allergic rhinitis with mast-cells (NARMA) and 10.3% non allergic rhinitis with eosinophils and mast-cells (NARESMA). Middle meatus cytology was in accordance with inferior turbinate cytology in only 37.6% of cases. Eosinophils and mast-cells were detectable more frequently in middle meatus samples (49.5% vs 19.6%, p < 0.01, 59.8% vs 29.9%, p < 0.01, respectively). 93.3% of NINAR patients received an inflammatory NAR phenotype at middle meatus cytology: 26.7% NARES, 24.4% NARNE, 31.1% NARMA and 11.1% NARESMA., Conclusion: Middle meatus cytology is more reliable than inferior turbinate cytology in phenotyping patients with NAR. Our study strengthen that nasal cytology should be implemented in clinical practice collecting samples at the middle meatus level., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Multifocal fibrosing thyroiditis (MFT) is an enigmatic entity, characterized by multiple fibrotic scar-like lesions with a paucicellular fibrotic center surrounded by a cellular peripheral area with reactive-appearing follicular cell atypia and variable chronic inflammation. Although poorly recognized and likely underreported in surgical pathology, the entity is considered rare with only 65 cases to date-including the current one reported to expand on the preoperative findings of this under-recognized entity. The average age of the patients is 46.8 years (range 15-71 years), 94% are female, with female to male ratio of 15:1. Individual MFT lesions typically have a superficial location. The average number of fibrotic lesions is 15.4 (range 2-51 per MFT case). Their average size is 3.1 mm (range 0.4-15.1). MFT is a disorder of diseased thyroids, typically found postoperatively in glands removed for other reasons, such as chronic lymphocytic/Hashimoto thyroiditis (32.3%), follicular nodular disease (nodular hyperplasia) (30.1%), hyperthyroidism/diffuse hyperplasia (Graves disease) (9.2%). Intriguing is the association with papillary thyroid carcinoma-present in 38.5% of MFT cases, and particularly with sub-centimetric and multifocal papillary thyroid carcinoma, with which MFT can be confused. Cases where MFT is the only thyroid pathology (7.7%) can be preoperatively mistaken for papillary thyroid carcinoma, due to worrisome ultrasound (US) and cytologic features, both of which are here documented for the first time as a component of this article. Wider recognition of MFT and of its cytologic and ultrasound features at preoperative evaluation may reduce unnecessary thyroidectomies., (© 2022. The Author(s).)

Variable internal jugular vein anatomy is not rare. A high jugular bulb (JB) is reported in 6 to 34% of cases and, it can be jeopardized during middle ear surgery, especially if dehiscent. Its injury represents a threatening complication of ear surgery. In recent years there has been an increasing trend in the use of endoscopic ear surgery for a wide range of otologic procedures, but being a one-hand technique, the management of bleeding still represents a challenge. The aim of this video, http://links.lww.com/MAO/B280 is to report the endoscopic surgical management of internal jugular vein hemorrhage during endoscopic type I tympanoplasty., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Objective: The aim of the present study was to illustrate the learning curve of endoscopic type-1 tympanoplasty comparing experts in microscopic otology versus neophyte surgeons., Methods: Eight ear surgeons, from tertiary referral centers, who had performed at least 30 endoscopic type 1 tympanoplasties were included in the study. Demographic data and medical records regarding the first 30 endoscopic type-1 tympanoplasties were retrospectively collected by each surgeon. A 14-questions survey focused on subjective aspects of the learning curve was administered. Surgeons were divided in two groups: one with previous experience in microscopic ear surgery (group 1) and one with no previous experience in ear surgery (group 2). The learning curve of endoscopic type 1 tympanoplasty was compared between the groups., Results: Mean surgical time was 89.2 min in group 1 vs. 79.5 min in group 2 (p < 0.01). When divided in 5 surgeries-steps, the only significant difference was appreciated in the first 5 surgeries with a longer mean time in group 1 vs. group 2 (+28.4 min; p < 0.05)., Conclusions: Surgeon's previous experience may influence the EES learning curve. Our results show that the first 5 surgical procedures are more challenging for surgeons experienced in microscopic surgery, subsequently the curve progression improves sharply and appears reversing the initial trend by the end of the 30 surgeries., Competing Interests: Declaration of Competing Interest The authors have not any financial support or relationship that may pose a conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: To investigate and compare the effect of endoscopic and microscopic type 1 tympanoplasty on the cochlear function, to determine if they have a different impact on the inner ear function., Methods: 72 ears treated by transcanal endoscopic type 1 tympanoplasty and 84 ears treated by microscopic type 1 tympanoplasty in 3 tertiary referral centers were enrolled in the study. Microscopic type 1 tympanoplasty were performed by transcanal or retroauricular approach. Only patients with mobile and intact ossicular chain were involved in the study. A retrospective chart review was performed. Main outcome measures were: (1) change in bone conduction thresholds at 250, 500, 1000, 2000, 4000 Hz; (2) change in bone conduction Pure Tone Audiometry; (3) correlation of audiometric outcomes with surgical technique, graft type and graft position., Results: A mild postoperative bone conduction threshold shift was observed at 2000 Hz and 4000 Hz in both groups, without significant differences between the two groups. No statistically significant modifications in bone conduction were observed at any frequencies in patients operated by transcanal endoscopic approach compared with those who underwent transcanal or retroauricular microscopic type 1 tympanoplasty. Moreover, neither the placement nor the type of the graft seemed to influence the cochlear function preservation., Conclusions: The endoscopic and the microscopic approaches have a similar impact on the bone conduction threshold during type 1 tympanoplasty. In particular, the one-handed manipulation of the ossicular chain during the endoscopic technique did not show an increased risk of inner ear damage.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has presented unprecedented challenges to the healthcare systems in almost every country around the world. Currently, there are no proven effective vaccines or therapeutic agents against the virus. Current clinical management includes infection prevention and control measures and supportive care including supplemental oxygen and mechanical ventilatory support. Evolving research and clinical data regarding the virologic SARS-CoV-2 suggest a potential list of repurposed drugs with appropriate pharmacological effects and therapeutic efficacies in treating COVID-19 patients. In this review, we will update and summarize the most common and plausible drugs for the treatment of COVID-19 patients. These drugs and therapeutic agents include antiviral agents (remdesivir, hydroxychloroquine, chloroquine, lopinavir, umifenovir, favipiravir, and oseltamivir), and supporting agents (Ascorbic acid, Azithromycin, Corticosteroids, Nitric oxide, IL-6 antagonists), among others. We hope that this review will provide useful and most updated therapeutic drugs to prevent, control, and treat COVID-19 patients until the approval of vaccines and specific drugs targeting SARS-CoV-2., (© Springer Nature Switzerland AG 2020.)

Type II diabetes is an established cause of vascular impairment. Particulate air pollution is known to exacerbate cardiovascular and respiratory conditions, particularly in susceptible populations. This study set out to determine the impact of exposure to traffic pollution, with and without particle filtration, on vascular endothelial function in Type II diabetes. Endothelial production of nitric oxide (NO) has previously been linked to vascular health. Reactive hyperemia induces a significant increase in plasma nitrite, the proximal metabolite of NO, in healthy subjects, while diabetics have a lower and more variable level of response. Twenty type II diabetics and 20 controls (ages 46-70 years) were taken on a 1.5 hr roadway traffic air pollution exposure as passengers. We analyzed plasma nitrite, as a measure of vascular function, using forearm ischemia to elicit a reactive hyperemic response before and after exposure to one ride with and one without filtration of the particle components of pollution. Control subjects displayed a significant increase in plasma nitrite levels during reactive hyperemia. This response was no longer present following exposure to traffic air pollution, but did not vary with whether or not the particle phase was filtered out. Diabetics did not display an increase in nitrite levels following reactive hyperemia. This response was not altered following pollution exposure. These data suggest that components of acute traffic pollution exposure diminish vascular reactivity in non-diabetic individuals. It also confirms that type II diabetics have a preexisting diminished ability to appropriately respond to a vascular challenge, and that traffic pollution exposure does not cause a further measureable acute change in plasma nitrite levels in Type II diabetics.

A 39-year-old male reported fevers, weight loss, watery loose stools, and decreased visual acuity in his right eye over the prior five years. He was pancytopenic, had an elevated American council on exercise level, total bilirubin, and alkaline phosphatase. Computed tomography revealed massive hepatosplenomegaly and emphysematous lung changes. Liver biopsy showed non caseating granulomas. The patient was diagnosed with extrapulmonary sarcoidosis and was treated with prednisone. The patient symptomatically improved but 5 mo later presented with abdominal pain caused by perforation of the cecum. He underwent a cecectomy and pathology revealed pneumatosis cystoides intestinalis. This represents the first reported association between pneumatosis cystoides intestinalis and sarcoidosis. The etiology of pneumatosis cystoides intestinalis in this case was likely multifactorial and involved both effects of the corticosteroids as well as the advanced nature of the gastrointestinal sarcoidosis. Furthermore this case has the unique features of emphysematous lung changes and pancytopenia which are uncommon with sarcoidosis.

Thyroid carcinomas are an uncommon entity in childhood. We report a case of papillary thyroid cancer presenting as Horner syndrome in a 14 year-old child, which is the only reported such case in the pediatric population., (Copyright 2010 Wiley-Liss, Inc.)

Recurrent lumbar disk herniation is the most common complication following primary open diskectomy. It is defined as recurrent back and/or leg pain after a definite pain-free period lasting at least 6 months from initial surgery. Careful neurologic examination is critical, and laboratory tests should be ordered to evaluate for infection. Imaging demonstrates disk herniation at the previously operated level. It is important to differentiate recurrent disk herniation from postoperative epidural scar because the latter may not benefit from reoperation. Treatment of recurrent lumbar disk herniation includes aggressive medical management and surgical intervention. Surgical techniques include conventional open diskectomy, minimally invasive open diskectomy, and open diskectomy with fusion. Fusion is necessary in the presence of concomitant segmental instability or significant foraminal stenosis resulting from disk space collapse.

Objective: To pilot a protocol to evaluate acute cardiovascular effects in in-vehicle exposure to traffic air pollutants in people with diabetes., Methods: Twenty-one volunteers with type 2 diabetes were passengers on 90- to 110-minute car rides on a busy highway. We measured in-vehicle particle number and mass (PM2.5) nitrogen dioxide, and carbon monoxide and heart rate, heart rate variability (HRV), and blood pressure., Results: Compared with pre-ride measurements, we found a decrease in high frequency (HF) HRV from pre-ride to next day (ratio 0.66, 95% CI = 0.47 to 0.93) and an increase in low frequency to HF ratio at post-ride (ratio 1.92, 95% CI = 1.21 to 3.05) at post-ride. Interquartile range increases in measured pollutants were associated with next-day decreases in HR HRV., Conclusions: This protocol appears useful for assessing acute adverse cardiovascular effects of in-vehicle exposures among people who have diabetes.

Conclusions: Our results confirm that supracricoid laryngectomies (SL) are reliable techniques for glottosupraglottic tumors, even for selected T3 and T4 cases, if the indications are correct. These surgical techniques allow a good quality of life with the preservation of the larynx., Objective: SL with cricohyoidoepiglottopexy (CHEP) and cricohyoidopexy (CHP) have been popular over the last 20 years for the treatment of the glottic and/or supraglottic squamous cell carcinoma due to demonstrated good oncological and functional results. We report our experience with these techniques, with special focus on long-term oncological and functional results., Patients and Methods: We retrospectively reviewed 206 patients who had undergone SL with CHEP or CHP technique between 1987 and 1998 for glottosupraglottic squamous cell carcinoma in our department. The long-term results for 206 patients with T1-T4 laryngeal carcinomas treated with SL are reported: 90.8% CHEP and 9.2% CHP. The mean follow-up was 62 months., Results: Oncological results: the 5-year actuarial disease-free survival was 85%; the 5-year determinate actuarial survival was 88.3%. Functional results: organ preservation rate was 97%. Phonation was assessed according to the GRBAS scale.

The purpose of our study was to examine the relationship between insulin resistance and blood pressure during pregnancy and to determine to what extent insulin resistance is related to the subsequent development of pregnancy-induced hypertension. The study population consisted of 292 women who had serum insulin, glucose and insulin-glucose ratios determined at 26-28 weeks gestation in a fasting state and 1 hr after a 50-g oral glucose challenge. These were compared with blood pressures at 26-28 weeks gestation and in the late third trimester. A statistically significant correlation exists overall between (1) blood pressure at 26-28 weeks gestation and both fasting insulin and insulin-glucose ratios, as well as (2) systolic blood pressure at term and fasting insulin levels. However, when controlled for confounding variables including body mass index, race and age, no statistically significant relationship remained. The metabolic variables in patients with pregnancy-induced hypertension were not statistically different from the normotensive patients. In conclusion, this study demonstrates that insulin resistance and hyperinsulinemia are not major determinants of blood pressure during pregnancy.

Malignant external otitis (MEO) is an infrequent but severe infective disorder, generally due to Pseudomonas aeruginosa, which most often affects elderly diabetics patients. The clinical features rarely permit exact diagnosis of MEO to be made promptly, and initially at least they are difficult to distinguish from those of external otitis. This explains the frequent delay in diagnosis with respect to the onset of symptoms. Physical examination almost always reveals the presence of aspecific granulation tissue in the external auditory canal, while the most common laboratory finding is raised erythrocyte sedimentation rate (ESR). Imaging has great diagnostic relevance: CT and MRI are very useful for spatial resolution, while radionuclide scanning and, in our experience, SPECT are superior for detecting early osteitis and monitoring response to therapy. We present an extensive review of the literature and our personal experience. In particular, we stress the relevance of immunological study of MEO patients: all our 4 patients had defective immune defences. As regards therapy, like other authors we underline the fundamental importance of long-term antibiotic treatment. The availability of quinolones and latest generation cephalosporins has greatly simplified the choice of antibiotic treatment, although clinicians should be aware of the possibility of drug-resistant bacterial strains.

Seventy-four patients with plasma low-density lipoprotein cholesterol levels > or = 160 mg/dl after an American Heart Association phase 1 diet were randomized to double-blind treatment with fluvastatin, 20 mg/day, or placebo for 6 weeks. Immediate-release niacin was then added to both treatment regimens and titrated to a maximum of 3 g/day for a further 9 weeks. After 6 weeks of fluvastatin monotherapy, low-density lipoprotein cholesterol levels decreased by 21% (p < 0.001 vs placebo), and after the addition of niacin, response was potentiated to 40% compared with 25% for the niacin control group at study end point (p < 0.001). Fluvastatin, alone and in combination with niacin, also significantly improved high-density lipoprotein cholesterol (increases of about 30%) and triglyceride profiles (decreases of approximately 28%) from baseline. Lipoprotein(a) decreased by 37% in those receiving fluvastatin-niacin but was unaltered in those receiving fluvastatin alone. No serious adverse events were ascribed to fluvastatin, and no cases of myositis were observed. Small, transient, asymptomatic increases in aspartate aminotransferase were noted with fluvastatin-niacin treatment but were not considered clinically relevant. Although the fluvastatin-niacin combination in this study was without evidence of significant transaminitis, myopathy, or rhabdomyolysis, it would seem prudent to continue to monitor its safety with longer term use. In conclusion, fluvastatin, both as monotherapy and in combination with niacin, proved to be an effective, safe, and well-tolerated therapeutic alternative for hypercholesterolemia.

A double-blind, randomized study was undertaken to evaluate the efficacy and safety of fluvastatin as monotherapy and as combination therapy with niacin in the treatment of hypercholesterolemia refractory to diet. Seventy-four patients with plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 160 mg/dL were treated with fluvastatin, 20 mg/d, or placebo for 6 weeks. Thereafter, immediate-release niacin, at a dosage titrated to a maximum of 3 g/d, was added to both regimens for another 9 weeks. All adverse events were monitored, with particular attention to the evaluation of liver and muscle enzymes. Initial analysis of the data shows that fluvastatin and its combination with niacin was well tolerated and was not associated with any serious adverse events. Small, transient, asymptomatic rises in aspartate aminotransferase (AST) occurred in 28.9% of fluvastatin-niacin treated patients compared to 8.3% in the niacin-placebo control arm (p < 0.05). These were considered clinically insignificant in that no transaminase elevations > 3 times the upper limit of normal occurred. No evidence of myopathy, creatine kinase levels exceeding 10 times the upper limit of normal, myositis, or rhabdomyolysis were demonstrated in this short-term trial. The majority of adverse events resulting in patient withdrawals were ascribed to niacin therapy and included cutaneous vasodilatation, flushing, itching, and rash. These preliminary results suggest that fluvastatin, both alone and combined with niacin, is an effective, safe, and well-tolerated treatment for hypercholesterolemia.

The effect of gambling and gaming on plasma levels of uric acid was studied. Blood samples were obtained from normal subjects while they gambled for money or while they played checkers without betting. There was an interaction of time and activity reflecting primarily an association of increased uric acid levels during gambling over time, compared with gaming and relaxation. This indicates that gambling can increase plasma levels of uric acid.

Pravastatin, a competitive inhibitor of hydroxymethylglutaryl CoA reductase (HMG CoA reductase) is a potent hypocholesterolemic agent in humans as well as experimental animals, including the Watanabe heritable hyperlipidemic (WHHL) rabbit, lacking low density lipoprotein (LDL) receptor activity. We studied the effect of pravastatin on several aspects of cholesterol metabolism in WHHL rabbits. Cholesterol synthesis was measured by intraperitoneal injection of radioacetate and determination of its incorporation into the nonsaponifiable lipid fraction of liver, plasma, adrenal glands and gonads. A single dose of pravastatin (25 mg/kg) caused statistically significant inhibition of hepatic cholesterol synthesis at 2, 6, 12, and 24 hours following oral administration. By 48 hours, the inhibitory effect of the drug was no longer demonstrable. The pattern of radioactivity in the plasma was similar to that in the liver. The drug had no statistically significant effect on cholesterol synthesis in adrenal glands and gonads, suggesting a selective effect on the liver. Cholesterol absorption was studied after simultaneous oral administration of [3H] cholesterol and [14C] beta-sitosterol. Pravastatin, 50 mg/kg for 10 days had no effect on fecal excretion of the radiolabelled steroids over 4 days. At 24 hours the plasma level of [14C] cholesterol was 1/3 that of control in pravastatin treated animals (p < 0.05) but did not undergo an accelerated decline over 6 days. The activity of acyl CoA: cholesterol acyltransferase (ACAT) in intestinal mucosa and the concentration of hepatic cholesterol were similar in animals treated over one year with pravastatin 50 mg/kg/day or with placebo. Our data do not allow us to make definitive conclusions about the effect of pravastatin on cholesterol absorption but are compatible with the hypothesis that the drug inhibits the hepatic synthesis as well as the assembly of cholesterol into lipoproteins.

The effects of long term administration of pravastatin (a competitive inhibitor of hydroxymethylglutaryl CoA reductase) were assessed by measuring serum lipids and aortic and coronary atherosclerosis in Watanabe Heritable Hyperlipidemic (WHHL) rabbits. Six-month-old WHHL rabbits were given either 50 mg/kg/day of the drug or vehicle. The rabbits were sacrificed following 6 or 12 months of treatment and serum cholesterol and triglycerides and aortic cholesterol and hydroxyproline were measured. Atherosclerotic plaques in the aorta and coronary arteries were quantified with morphometric methods. Mean serum cholesterol +/- SEM (n) in the control vs. pravastatin groups after 6 months were: 535 +/- 34 (11) vs. 411 +/- 22 (12) (p less than 0.005) and after 12 months 458 +/- 43 (9) vs. 309 +/- 29 mg/dl (12) (p less than 0.005). In the pravastatin group, percent aortic area covered with plaque and aortic cholesterol content were reduced 35% (ns) and 55% (p less than 0.05) at 6 months, and 26% (ns) and 44% (ns) at 12 months, respectively. Little difference was found in serum triglycerides and aortic hydroxyproline in the 2 groups. There was strong correlation of serum cholesterol with aortic cholesterol content (r = 0.61, p less than 0.003) and with the percent aortic plaque area (r = 0.67, p less than 0.001), at 12 months. Morphometric analysis of wall thickness and lumen area of major coronary arteries revealed no significant differences in the 2 groups. In conclusion, pravastatin effectively lowered the serum cholesterol level in an animal model defective in low density lipoprotein receptors; this reduction was strongly correlated with amelioration of such atherosclerotic processes as lipid deposition and plaque formation.

It has been suggested that liver allografts are less sensitive to lymphocytotoxic antibodies than other organ allografts. In this experimental study in sensitized inbred rat recipients, we have used extracorporeal liver hemoperfusion to study interactions between the liver and lymphocytotoxic antibodies. Donor-specific liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. Immunofluorescence examination of the hemoperfused liver revealed deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. In control rats in which a third-party liver, a donor-specific splenic or renal hemoperfusion was performed, heart allograft survival was less prolonged. The decrease in antibody levels was not significant and the deposit of C3 and IgG was much less evident. Similarly, previous blockade of the Kupffer cells of the donor-specific hemoperfused liver by dextran sulfate suppressed the effect of liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies onto nonparenchymal liver cells.

The aorta and the kidney of 12 month old hyperlipidemic WHHL and obese Zucker rats, were examined morphologically. The WHHL developed severe and premature atherosclerosis but did not develop glomerulosclerosis. In contrast, the Zucker rats did not manifest atherosclerosis of the aorta, but developed glomerulosclerosis. These two animal models could be useful in understanding the roles of heterogeneous lipoprotein particles, genetic susceptibility, hemodynamic stress, and mesangial interactions with lipoproteins in the development of glomerulosclerosis.

The many patients with mild, asymptomatic hypercalcemia identified by automated methods of clinical chemistry pose a challenge to the clinician. Which of them are likely to develop manifestations of primary hyperparathyroidism?

Cultured skin fibroblasts from two patients with homozygous familial hypercholesterolemia and three normal subjects were preincubated for 24 hours in medium containing 10% delipidated serum with insulin concentrations of 0.4, 4, or 40 ng/mL. [14C]acetate incorporation into total lipids, cholesterol, and phospholipids was significantly increased in familial hypercholesterolemic cells at insulin concentrations of 0.4 and 4 ng/mL, which had no effect in normal cells. When the data were normalized as percent stimulation over control for individual experiments, [14C]acetate incorporation into cholesterol was comparable at 40 ng/mL in both cell types. Similar results were obtained in cells preincubated in serum free artificial medium. Coordinate increases in the activity of 3-hydroxy-3-methylglutaryl CoA reductase in response to insulin were not found. These studies show that familial hypercholesterolemic cells have an altered lipogenic response to low concentrations of insulin.

Liver allografts have a privileged status in regard to acute rejection. In this experimental study, we have analyzed the immunosuppressive effects of an extracorporeal liver hemoperfusion. In the LEW-to-BN combination of inbred rats, donor-specific liver hemoperfusion can significantly delay acute rejection of heart allografts. Analysis of the immunological status of these animals revealed a significant decrease in donor-specific lymphocytotoxic antibodies and in cytotoxic T lympholysis. Reactivity in mixed lymphocyte culture was normal. After third-party (DA) liver hemoperfusion or after donor-specific (LEW) splenic hemoperfusion, prolongation of heart allograft survival was moderate. Previous blockade of Kupffer cells suppressed the effects of donor-specific liver hemoperfusion. These results suggest that the sequestration by Kupffer cells of a clone of cytotoxic T cells and/or lymphocytotoxic antibodies may explain the immunosuppressive effects of donor-specific liver hemoperfusion.

Adduction of ethylene glycol moieties to the 3-hydroxy position of cholesterol produces polyoxyethylated cholesterol (POEC), a water-soluble compound that suppresses cholesterol synthesis and esterification in cultured human fibroblasts. Feeding Sprague-Dawley rats a diet containing 2% (wt/wt) POEC with 10 ethoxy groups resulted in a 3-fold increase in hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity compared to activity in rats pair-fed a diet of standard rat chow. POEC with an average of 20 ethoxy groups (POEC-20) caused comparable changes in hepatic [2-14C]acetate incorporation into non-saponifiable lipids under ad libitum feeding conditions, significantly reduced cholesterol absorption (18% vs 57%), and increased fecal excretion of neutral steroids (5.1 vs 2.0 mg/g food intake). POEC-20 also reduced cholesterol absorption in rats fed a diet enriched with 2% cholesterol (11% vs 31%). Histologic studies of intestinal mucosa and hepatic tissues from rats fed POEC showed no pathologic changes. These experiments indicate that POEC reduces cholesterol absorption and causes compensatory increases in hepatic cholesterol synthesis.

Experimental evidence suggests a central-nervous-system origin of Cushing's disease and a role for serotonin in the regulation of ACTH release. The efficacy of cyproheptadine therapy, therefore, was studied in three patients with such disease. Administration of 24 mg daily over a period of three to six months was associated with prompt and sustained clinical and laboratory remission. Lessening of the physical manifestations of hypercorticism occurred, together with marked improvement in muscular weakness. Urinary corticosteroid excretion and cortisol secretory rate returned to normal. The urinary corticosteroid response to dexamethasone (2 mg per day) became normal; a paradoxical increase followed 8 mg per day. Abnormal circadian periodicity of plasma cortisol concentrations persisted. Return of normal amounts of Stage III to IV sleep occurred in the one patient so studied, who previously had markedly decreased periods of these stages. Discontinuance of therapy in one patient was associated with return of laboratory evidence of hypercorticism.

Although imaging techniques have improved greatly in recent years, plain radiography remains the initial imaging method for evaluation of patients with low back pain. The sacrum, in particular, is a difficult structure to evaluate. In reviewing 12 cases, the authors found an unacceptably high rate of missed sacral metastases (83%). Using a photograph and a radiograph of two bony pelvic specimens to represent normal anatomy and the normal appearance of the sacral foraminal lines, sacral destruction is illustrated in six cases. All lesions were neoplastic and most were metastatic. In each case there was destruction of one or more sacral lines. The importance of careful observation for symmetric appearance of these lines is emphasized.

A 24-year-old woman with non-pituitary dependent Cushing's syndrome was found to have bilateral adrenal myelolipomas at surgery. These benign tumors consist of bone marrow and fat and are uncommon incidental findings that are discovered by computed tomography. Myelolipomas have rarely been associated with Cushing's syndrome, but the cause of the syndrome has not always been defined, because the reports preceded modern diagnostic methods. Careful examination of the adrenal glands from our patient showed a fusion of myelolipoma elements and adrenal cells without distinct adenomas or the typical nodular pattern of adrenal hyperplasia. This report suggests that adrenal myelolipomas and atypical hyperplasia of the zona fasciculata may be anatomically and functionally related.