Global transcriptional differences in myokine and inflammatory genes in muscle of mature steer progeny are related to maternal lactation diet and muscle composition.

Steer progeny suckled by cows fed a dried distillers grains and solubles (DDGS) diet the first 3 mo of lactation were heavier during feedlot finishing and had significantly lower marbling and larger longissimus muscles than steers suckled by cows fed a control diet (CON). These differences were profound in that progeny were managed and fed identically from weaning until finishing, and findings suggest that the suckling period established the developmental program of muscle composition. Here transcriptomes of longissimus muscle were measured by next-generation sequencing to investigate whether there were any developmental clues to the differences in marbling scores and muscle content between steers suckled by DDGS ( n = 5) vs. control (CON; n = 5) diet-fed cows during lactation. There were 809 genes differentially expressed ( P-adj<0.1) between CON and DDGS muscle. Of these 636 were upregulated and 173 downregulated in DDGS relative to CON. Overall the DDGS vs. CON muscle transcriptomic signature was promyogenic and antiadipogenic. In particular, myokines/satellite cell maintenance factors were found among upregulated (LIF, CNTF, FGFB1, EPHB1) genes. The antiadipogenic signature was typified by the upregulation of anti-inflammatory cytokines and receptors (IL1RAP, IL1RL2, IL13RA2, IL1F10), and downregulation of expression of inflammation/inflammatory cytokines and receptor (TNF, IL6R, CXCL9), which suggests a selection of differentiation pathways away from adipogenic line. The upregulation of TGFB, SPP1, and INHBA supports selection of fibroblast lineage of cells. Thus, the lactation phase of production can effect meat quality by affecting transcriptional signatures that favor myogenesis and depress inflammation.

Increased daily movement associates with reduced mortality among COPD patients having systemic inflammation.

BACKGROUND: Emerging research demonstrates an interrelationship between systemic inflammation, physical activity and premature all-cause mortality among chronic obstructive pulmonary disease (COPD) patients. Less common in this literature is the use of objective measures of physical activity and representative samples of COPD patients. OBJECTIVE: To examine the association between objectively measured physical activity and all-cause mortality among a national sample of COPD patients, with stratification by inflammatory status. METHODS: Data from the 2003 to 2006 NHANES were employed, with follow-up through 2011. Physical activity was objectively measured via accelerometry; COPD was assessed via physician-diagnosis; and inflammation was assessed via C-reactive protein (CRP) levels from a blood sample. RESULTS: Analysis included 385 adults (20+ years) with COPD. The median follow-up period was 78 months (IQR = 64-90), with 82 COPD patients dying during this period. After adjustment, physical activity was not associated with all-cause mortality among the entire sample (HR = 0.80; 95% CI: 0.61-1.05) or those with no systemic inflammation (HR = 0.89; 95% CI: 0.63-1.24). However, for every 60 min increase in physical activity per day, COPD patients with elevated CRP had a 31% reduced risk of all-cause mortality (HR = 0.69; 95% CI: 0.51-0.93). CONCLUSION: Physical activity may help to promote survival among COPD patients, particularly those with elevated inflammation.

Pulmonary sensory and reflex responses in the mouse.

Mouse model research is proliferating because of its readiness for genetic manipulation. Little is known about pulmonary vagal afferents in mice, however. The purpose of this study was to determine whether their pulmonary afferents are similar to those in large animals. Single-unit activity was recorded in the cervical vagus nerve of anesthetized, open-chest, and mechanically ventilated mice. We evaluated airway sensory activity in 153 single units; 141 were mechanosensitive, with 134 inflation receptors and 7 deflation receptors. The remaining 12 receptors were chemosensitive and mechanically insensitive, showing low basal firing frequency and behaving like C-fiber or high-threshold Adelta-receptors. In separate studies, phrenic activity was recorded as an index of respiratory drive to assess pulmonary reflexes. Lung inflation produced a typical Hering-Breuer reflex, and intravenous injection of phenylbiguanide produced the typical chemoreflex resulting in apnea, bradycardia, and hypotension. These reflexes were blocked by bilateral vagotomy. We conclude that mice possess a similar set of airway sensors and pulmonary reflexes as typically found in larger animals.

Water and solute mass balance of five small, relatively undisturbed watersheds in the U.S.

Geochemical mass balances were computed for water years 1992-1997 (October 1991 through September 1997) for the five watersheds of the U.S. Geological Survey Water, Energy, and Biogeochemical Budgets (WEBB) Program to determine the primary regional controls on yields of the major dissolved inorganic solutes. The sites, which vary markedly with respect to climate, geology, physiography, and ecology, are: Allequash Creek, Wisconsin (low-relief, humid continental forest); Andrews Creek, Colorado (cold alpine, taiga/tundra, and subalpine boreal forest); Río Icacos, Puerto Rico (lower montane, wet tropical forest); Panola Mountain, Georgia (humid subtropical piedmont forest); and Sleepers River, Vermont (humid northern hardwood forest). Streamwater output fluxes were determined by constructing empirical multivariate concentration models including discharge and seasonal components. Input fluxes were computed from weekly wet-only or bulk precipitation sampling. Despite uncertainties in input fluxes arising from poorly defined elevation gradients, lack of dry-deposition and occult-deposition measurements, and uncertain sea-salt contributions, the following was concluded: (1) for solutes derived primarily from rock weathering (Ca, Mg, Na, K, and H(4)SiO(4)), net fluxes (outputs in streamflow minus inputs in deposition) varied by two orders of magnitude, which is attributed to a large gradient in rock weathering rates controlled by climate and geologic parent material; (2) the net flux of atmospherically derived solutes (NH(4), NO(3), SO(4), and Cl) was similar among sites, with SO(4) being the most variable and NH(4) and NO(3) generally retained (except for NO(3) at Andrews); and (3) relations among monthly solute fluxes and differences among solute concentration model parameters yielded additional insights into comparative biogeochemical processes at the sites.

Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

BACKGROUND: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). METHODS AND RESULTS: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). CONCLUSIONS: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

Enalapril in low-renin essential hypertension.

The antihypertensive efficacy of N-[(S)-1-(ethoxycarbonyl)-3-phenyl-propyl]-L-alanyl-L-proline (enalapril maleate) was evaluated in a randomized, double-blind trial in 23 patients with mild low-renin essential hypertension ranging in age from 32 to 70 yr (20 were black and 3 were white). All underwent a 4-wk washout-placebo phase and were then assigned to a dosing schedule of either 10 mg enalapril once daily, 5 mg enalapril twice daily, or placebo twice daily for 12 wk. Conditional on diastolic pressure, the dose was increased at 4-wk intervals to a maximum of 40 mg daily or until control was achieved or the end of the study reached. At the end of the 12-wk titration phase, there was a follow-up period during which measurements were made after discontinuation of the medication. Mean supine diastolic pressure decreased from baseline (98.5 +/- 2.6 mm Hg) during the titration phase (86.3 +/- 4.6 mm Hg) in the group taking enalapril once daily. In three of the eight patients in the once-daily group and five of eight in the twice-daily group, supine diastolic pressures fell below 90 mm Hg. Neither supine nor standing systolic pressure nor standing diastolic pressure decreased significantly from pretreatment levels during enalapril once or twice daily. Heart rates measured after 5 min supine rest were not altered by enalapril. Enalapril induced inhibition of converting enzyme activity at all dose levels and with both dosing schedules. No adverse effect attributable to enalapril occurred during the study. The data indicate that once-daily enalapril is safe and effective treatment for mild low-renin essential hypertension.

Simvastatin: the clinical profile.

Simvastatin is the second in the class of compounds known as hydroxy-methylglutaryl-coenzyme A reductase inhibitors to be extensively studied in humans. The drug has now been given to over 1,800 patients with primary hypercholesterolemia for periods of up to two years. In the range of dosage from 10 to 40 mg once daily, therapy is associated with reductions of up to 30 percent in total cholesterol and 40 percent in low-density lipoprotein cholesterol levels, as well as with increases of approximately 10 percent in high-density lipoprotein cholesterol levels. The most common clinical adverse experiences are mild gastrointestinal effects and headache, which seldom require discontinuation of therapy. Elevations of creatine kinase (skeletal muscle isoenzyme) levels to more than three times the upper limit of the normal range have been seen in about 3 percent of patients, but also have seldom required discontinuation of therapy. Conversely, elevations of hepatic transaminase levels to more than three times the upper limit of the laboratory normal range have been seen in about 1.5 percent of patients and have caused discontinuation of therapy in 0.6 percent of patients treated. Simvastatin appears to be an effective and well-tolerated agent for the treatment of primary hypercholesterolemia and, as further study confirms long-term safety and efficacy, it should become a useful addition to the therapeutic armamentarium.

Comparison of low-dose simvastatin and gemfibrozil in the treatment of elevated plasma cholesterol. A multicenter study. The Simvastatin Study Group.

A 12-week, randomized, double-blind, multicenter study was undertaken to compare the efficacy, tolerability, and safety of simvastatin and gemfibrozil in 290 patients with primary hypercholesterolemia. Patients in stratum I (initial low-density lipoprotein cholesterol level less than 195 mg/dl) received simvastatin 5 to 10 mg once every afternoon; patients in stratum II (initial low-density lipoprotein cholesterol level at least 195 mg/dl) received 10 to 20 mg once every afternoon. Gemfibrozil was given in a constant dosage of 600 mg twice daily in both strata. Simvastatin reduced low-density lipoprotein cholesterol levels by 26 and 34 percent in strata I and II, respectively. The corresponding reductions brought about by gemfibrozil were 18 and 17 percent. High-density lipoprotein cholesterol was increased by 7 and 9 percent by simvastatin and by 17 and 16 percent by gemfibrozil in strata I and II, respectively. Ratios of low-density to high-density lipoprotein cholesterol were reduced by approximately 25 percent by simvastatin 5 to 10 mg once every afternoon and gemfibrozil 600 mg twice daily, but were reduced by 37 percent by simvastatin 10 to 20 mg once every afternoon. Both drugs reduced plasma triglyceride levels, but gemfibrozil was much more effective. The short-term tolerability and safety of both drugs appeared to be good during the 12-week study. The results suggest that both drugs have useful but distinctly different lipid-modifying properties.

Enalapril worldwide experience.

Overall, the worldwide experience on enalapril to date is very encouraging. The drug produces good to excellent responses in 54 to 66 percent of patients with essential hypertension and is at least as effective as either diuretics or beta blockers. The effects of enalapril compared with those of diuretics confirm that patients more dependent upon the renin-angiotensin system respond better. When hydrochlorothiazide is administered concomitantly with enalapril, almost all patients respond, with good long-term maintenance. In patients with severe hypertension, Blocadren or Aldomet may be added in addition to hydrochlorothiazide and will produce additional benefit. Enalapril attenuates the adverse metabolic effects of hydrochlorothiazide, particularly hypokalemia. Overall, although the efficacy of enalapril and that of captopril are similar, enalapril is better tolerated and does not appear to be associated with any significant occurrence of captopril-type side effects, particularly the skin rash and loss of taste. As expected, enalapril and other converting inhibitors may be associated with azotemia in patients with bilateral renovascular hypertension.

Hydroxymethylglutaryl coenzyme A reductase inhibitors as monotherapy in the treatment of hypercholesterolemia.

A variety of double-blind studies have compared the efficacy of hydroxymethylglutaryl coenzyme A reductase inhibitors (lovastatin and simvastatin) with that of control agents (cholestyramine, fibrates and probucol) in patients with type IIA or IIB primary hypercholesterolemia. Results have shown that both lovastatin and simvastatin are more effective than the standard therapies with regard to reducing total and low-density lipoprotein cholesterol. Decreases in triglycerides and increases in high-density lipoprotein cholesterol were generally greater with fibrates. Ongoing studies are assessing the benefits of lovastatin and simvastatin in reducing the incidence of mortality from coronary artery disease, as well as causing regression of coronary atheroma.

Long-term safety and efficacy profile of simvastatin.

Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, has been administered to approximately 2,400 patients with primary hypercholesterolemia with a mean follow-up of 1 year in controlled clinical studies and their open extensions. Approximately 10% of this population received simvastatin for a period of greater than or equal to 2 years. The population on whom this safety analysis is based had a mean age of 50 years; 62% were men and approximately 27% had preexisting coronary artery disease. Simvastatin was titrated to the maximal daily dose of 40 mg each evening in 56% of the study population (last recorded dose). The most frequently reported drug-related clinical adverse experiences were constipation (2.5%), abdominal pain (2.2%), flatulence (2.0%) and headaches (1%). Persistent elevations of serum transaminase levels greater than 3 times the upper limit of normal were observed in only 1% of this cohort with only 0.1% of the total population requiring discontinuation of therapy. There were no clinically apparent episodes of hepatitis. Discontinuation of therapy due to myopathy was extremely rare (0.08%). Only minimal increases in the frequency of lens opacities (1%) were observed from baseline to the last lens examination during follow-up, consistent with the expected increase in lens opacity development due to normal aging. Patients who were greater than or equal to 65 years old had a clinical and laboratory safety profile comparable to the nonelderly population.(ABSTRACT TRUNCATED AT 250 WORDS)

HMG CoA reductase inhibitors. Current clinical experience.

Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.

Enalapril in hypertension and congestive heart failure. Overall review of efficacy and safety.

Multiclinic controlled studies have shown that enalapril alone 10 to 40 mg/day orally is effective in lowering blood pressure in patients with essential hypertension. Enalapril has been compared with thiazides and beta-blockers (propranolol, metoprolol and atenolol). The effect on systolic blood pressure has been greater with enalapril than with beta-blockers. The proportion of patients who respond to enalapril alone with a decrease in diastolic blood pressure (greater than or equal to 10mm Hg) is around 70%. When a thiazide is added to the treatment, the proportion is above 90%. Enalapril improves the signs and symptoms associated with congestive heart failure. Patients increased their exercise tolerance by an average of 148 sec and improved in their NYHA cardiac status and prognosis classification. The overall incidence of side effects is similar to that seen in the placebo control groups. Side effects such as agranulocytosis, taste loss, rash, proteinuria were not characteristic of enalapril. This supports the hypothesis that the improved safety profile of enalapril is the result of being a nonsulphydryl angiotensin-converting enzyme (ACE) inhibitor. The most common side effects reported were dizziness, headache and asthenia. Abnormalities in electrolytes, uric acid, glucose or in lipids have generally not been associated with enalapril.

The effect of body fat distribution on pulmonary function tests.

Although the influence of obesity on pulmonary function tests has been examined, the role of body fat distribution has received limited attention. Pulmonary studies of patients severely affected by upper body obesity suggest they have more severely compromised lung volumes than obese patients with lower body obesity. We examined 42 healthy but normal or mildly obese men to determine if body fat distribution influences pulmonary function tests. Multiple measures of adiposity showed a significant inverse relationship with both spirometry and static lung volumes. However, the biceps skinfold thickness had the strongest inverse relationship with total lung capacity (TLC) compared to other anthropometric measures. The waist-to-hip ratio (WHR) demonstrated a significant inverse relationship with static lung volumes only when controlling for cigarette smoking. However, comparing pulmonary function tests between patients with a WHR less than 0.950 (lower body fat distribution) and subjects with a WHR of 0.950 or greater (upper body fat distribution) revealed that FVC, FEV1, and TLC were significantly lower in the patients with upper body fat distribution. Stepwise multiple regression analysis was done using all anthropometric variables and age which generated predictive equations that included the biceps skinfold thickness for residual volume (RV) and TLC. This suggests that upper body fat distribution may be associated with a modest impairment of lung volumes in normal and mildly obese men. Until the findings of this study can be applied to a larger, ethnically and anthropometrically diverse population, and to women, we believe caution is warranted when standard equations are used to predict pulmonary function tests in an anthropometrically diverse population.

Renal and cardiovascular response to nonhypotensive sepsis in a large animal model with peritonitis.

We studied the functional effects of intraperitoneal sepsis on systemic hemodynamics in general, and on renal function in particular, in sheep in whom bacterial peritonitis was induced by cecal perforation. In the first group of seven sheep (group 1) fluid was administered throughout the period of sepsis to maintain pulmonary capillary wedge pressure as close to presepsis values as possible. These sheep exhibited hemodynamic changes known to be associated with sepsis in man: increased cardiac output and decreased systemic vascular resistance. In a second group of seven sheep (group 2) fluid intake was restricted; compared with group 1, these sheep demonstrated a smaller increase in cardiac output that did not persist and that was associated with an increase in the systemic vascular resistance during the septic period. Plasma renin levels increased fivefold in group 2 but were unchanged in group 1. Serial renal biopsies during the septic period revealed that all sheep had evidence of tubular cell damage on electron microscopy: cell swelling, loss of the microvillous brush border, and cell necrosis. Both groups of sheep also demonstrated marked tubular proteinuria similar to that found in humans with generalized sepsis. Despite this, sheep in group 1 exhibited no functional renal changes: creatinine clearance levels rose slightly from control values, urine concentrating ability was unimpaired, and fractional excretion of sodium increased appropriately in response to a sodium load. In contrast, group 2 sheep exhibited a fall in creatinine clearance levels but fractional sodium excretion did not fall as would have been expected were renal function entirely normal. The results suggest that generalized "hyperdynamic" sepsis induces tubular cell damage and tubular proteinuria by an unknown mechanism. However, this does not necessarily produce renal impairment since the glomerular filtration rate does not fall unless volume contraction is also allowed to occur.

Bradykinin stimulates respiratory drive by activating pulmonary sympathetic afferents in the rabbit.

We recently identified a vagally mediated excitatory lung reflex by injecting hypertonic saline into the lung parenchyma (Yu J, Zhang JF, and Fletcher EC. J Appl Physiol 85: 1485-1492, 1998). This reflex increased amplitude and burst rate of phrenic (inspiratory) nerve activity and suppressed external oblique abdominal (expiratory) muscle activity. In the present study, we tested the hypothesis that bradykinin may activate extravagal pathways to stimulate breathing by assessing its reflex effects on respiratory drive. Bradykinin (1 microg/kg in 0.1 ml) was injected into the lung parenchyma of anesthetized, open-chest and artificially ventilated rabbits. In most cases, bradykinin increased phrenic amplitude, phrenic burst rate, and expiratory muscle activity. However, a variety of breathing patterns resulted, ranging from hyperpnea and tachypnea to rapid shallow breathing and apnea. Bradykinin acts like hypertonic saline in producing hyperpnea and tachypnea, yet the two agents clearly differ. Bradykinin produced a higher ratio of phrenic amplitude to inspiratory time and had longer latency than hypertonic saline. Although attenuated, bradykinin-induced respiratory responses persisted after vagotomy. We conclude that bradykinin activates multiple afferent pathways in the lung; portions of its respiratory reflexes are extravagal and arise from sympathetic afferents.

A comparison of enalapril and metoprolol as initial therapy for mild to moderate hypertension.

The safety and efficacy of step-one therapy with enalapril, a new angiotensin-converting enzyme inhibitor, and metoprolol were compared in a double-blind, multicenter study involving 150 patients who had mild to moderate essential hypertension. After a four-week period of placebo run-in, therapy was initiated with twice-daily administration of either 5 mg of enalapril (N = 75) or 50 mg of metoprolol (N = 75). Patients who did not achieve a supine diastolic blood pressure of less than 90 mm Hg after six weeks of enalapril (maximum dose = 40 mg/d) or metoprolol (maximum dose = 400 mg/d) had hydrochlorothiazide 50 mg/d added to their treatment regimen for an additional six weeks. Both treatments produced significant (P less than .001) mean reductions in supine and standing blood pressures after 2, 4, 6, 8, 10, and 12 weeks of active therapy. Maximum reductions from baseline values of supine blood pressure in enalapril-treated (-25/-16 mm Hg) and metoprolol-treated (-21/-15 mm Hg) patients were observed after 12 weeks of single- or double-drug therapy. Approximately two-thirds of the patients responded to single-drug therapy; when hydrochlorothiazide was added, response rates increased to 88% of the patients treated with enalapril and 80% of the patients treated with metoprolol. Enalapril produced a consistently greater reduction in systolic blood pressure. Blacks had a significantly smaller mean blood pressure response to both enalapril and metoprolol than did nonblacks. Metoprolol patients had significant mean pulse rate reductions; enalapril patients had no significant change. Four enalapril-treated and six metoprolol-treated patients discontinued treatment because of side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Enalapril in congestive heart failure: acute and chronic invasive hemodynamic evaluation.

Following hemodynamic evaluation using invasive and noninvasive methods, 73 patients were treated in an open, uncontrolled, multicenter study with single oral doses of enalapril maleate 1.25 to 40 mg until the optimal dose for each patient (based upon hemodynamic response) was achieved. Diuretics were withheld and reinstituted only if necessary. Hemodynamic measurements were made at 0 (predrug), 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdrug. Patients were discharged on their optimal dose, treated 1 to 4 months and then rehospitalized for repeat hemodynamic measurements. The optimal enalapril single dose was associated with the following mean peak responses: increased cardiac index 42% (SE = 6) and decreased pulmonary capillary wedge pressure 40% (SE = 3), systemic vascular resistance 39% (SE = 2), and mean arterial pressure 23% (SE = 1.5). These changes persisted during chronic therapy. Chronic treatment with enalapril also improved exercise capacity 40% (P less than 0.01), ejection fraction 18% (P less than 0.05) and clinical status (N.Y.H.A. functional class, P less than 0.01). Ten and 20 mg/day, taken as once- or twice-daily regimens, were the most commonly effective doses.

IgA nephritis with nephrotic range proteinuria.

Nephrotic range proteinuria is uncommon in patients with IgA nephritis. For this reason we compared the clinical and pathologic features in 63 non-nephrotic patients with those in 8 patients who had nephrotic range proteinuria at the time of biopsy. Both the mean age and the mean duration of the disease at the time of diagnosis were not significantly different in the 2 groups of cases. Significant associations were found between nephrotic range proteinuria and the following: the extent of glomerular hyalinization, the severity of interstitial fibrosis and tubular atrophy and the degree of foot process effacement and mesangial matrix increase. A significant association was also noted with nephrotic range proteinuria had elevated levels of serum creatinine on follow-up compared with 20% of non-nephrotic cases. The results of our study suggest that patients with nephrotic range proteinuria have a more severe type of IgA nephritis from the outset and that a marked degree of proteinuria is not merely a consequence of the duration of disease.

Tuberculosis affecting a cadaveric renal allograft.

Tuberculosis is one of the more serious infections complicating renal transplantation. Although the incidence appears to be low, a dose of prednisone greater than 10 mg daily has been associated with a more severe form of disease. A case of tuberculosis with renal allograft involvement is described with documented bacteriological and radiological involvement in which treatment was successful with anti-tuberculosis chemotherapy. Deterioration in renal function did not occur. The prophylaxis of patients undergoing transplantation with a history of tuberculosis and the features, diagnosis and treatment of tuberculosis affecting a renal allograft are discussed.