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Metabolic neutrality of combined verapamil-trandolapril treatment in contrast to beta-blocker-low-dose chlortalidone treatment in hypertensive type 2 diabetes.

OBJECTIVE: To investigate the metabolic, antihypertensive and albuminuria-modifying effects of a heart rate-modulating calcium antagonist-angiotensin converting enzyme inhibitor combination compared with those of a beta-blocker-low-dose diuretic combination in non-insulin-dependent diabetic hypertensives. DESIGN: A prospective randomized double-blind study. SUBJECTS AND METHODS: Twenty-four diabetics with diastolic blood pressure 90-115 mmHg without azotemia (plasma creatinine level < 150 mumol/l) were evaluated after 4 weeks receiving placebo and 12 weeks receiving treatment either with combined slow-release verapamil (retard formulation) and trandolapril (mean maintenance doses, 180 and 1.6 mg daily) or with atenolol and chlortalidone (71 and 18 mg daily). Insulin sensitivity (by the minimal model method of Bergman), additional metabolic variables, clinic blood pressure, ambulatory blood pressure profile and renal indices were assessed at the end of the placebo and active treatment phases. RESULTS: Compared with placebo, the two therapies produced similar decreases in mean supine clinic blood pressure [10 +/- 3 versus 11 +/- 3% (means +/- SEM)], upright clinic blood pressure (10 +/- 4 versus 11 +/- 4%) and ambulatory daytime blood pressure (9 +/- 2 versus 12 +/- 3%). However, although the verapamil-trandolapril combination was found to be metabolically neutral, the atenolol-chlortalidone combination aggravated insulin resistance [insulin sensitivity index, from (0.8 +/- 0.2) to (0.3 +/- 0.1) x 10(-4)/min per U per ml], increased the serum triglycerides level and decreased the high-density lipoprotein cholesterol and plasma potassium levels. Although both therapies tended to reduce 24 h albuminuria, this was significant for the verapamil-trandolapril treatment only. CONCLUSIONS: Because the effect of any antihypertensive drug, including diuretics and beta-blockers, on cardiovascular morbidity and on mortality in non-insulin-dependent diabetic patients is not known, rational treatment selection can presently be based only on surrogate end-points. Therefore, the triad of metabolic neutrality with antihypertensive and antiproteinuric efficacy supports combined verapamil-trandolapril as a potentially valuable therapy for hypertension accompanying diabetes mellitus.

Adrenergic beta-Antagonists↗

Nephritis associated with an infected peritoneovenous LeVeen shunt.

A patient with chronic active hepatitis and medically unmanageable ascites developed staphylococcal bacteremia after insertion of a peritoneovenous LeVeen shunt. The patient developed glomerulonephritis, manifested by moderate proteinuria, microscopic hematuria with red cell casts, azotemia, and evidence of complement activation. The protracted infection, urinary, and renal abnormalities subsided after removal of the LeVeen shunt and a 3-week course of antibiotics. The clinical course of this patient is typical of the immune-complex mediated glomerulonephritis that has been previously well described in hydrocephalic patients with chronically infected ventriculoatrial shunts.

Ascites↗

Treatment of hypertension: the place of angiotensin-converting enzyme inhibitors in the nineties.

The past decade has seen a shift in the strategy for hypertension treatment from stepped therapy--a highly structured monolithic series of steps--to recommendations for a more individualized selection of treatment. Severe hypertension is a clear indicator to bypass traditional steps. Demographic factors, such as age, gender, and race, are often cited, but have proved to be less helpful. Concomitant medical conditions and problems are very common and are more often the crucial determinants in the selection of antihypertensive therapy. Coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, and chronic obstructive pulmonary artery disease, anxiety, and depression are all common, and each has implications for the selection of antihypertensive therapy. Blood pressure reduction is a surrogate for reduction of cardiovascular risk, and therefore, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, mild hyperlipidemia, and insulin resistance, as additional risk factors in hypertension. Consideration of all these factors makes it possible to individualize antihypertensive therapy in most patients today.

Angiotensin-Converting Enzyme Inhibitors↗

Loop diuretic therapy in liver cirrhosis with ascites.

Medical treatment of ascites is aimed at reverting sodium retention, that is, at creating a negative sodium balance to relieve ascites. Bed rest and low-sodium diet induce the disappearance of ascites in about 10% of patients. Loop diuretics and aldosterone antagonists must be administered to the patients not responding to the previous regimen. Available evidence indicates that aldosterone antagonists are the first-choice drugs, as these substances are more effective than furosemide. Nevertheless, loop diuretics potentiate the effects of aldosterone antagonists. The reduced efficacy of furosemide in these patients, when compared with that of spironolactone, may be related to an impairment of both pharmacodynamics and pharmacokinetics. In fact, most sodium not reabsorbed in Henle's loop, due to the action of furosemide, is subsequently taken up in the distal nephron because of hyperaldosteronism. A further mechanism of resistance may be related to an impaired excretion of furosemide into the tubular lumen. The use of diuretics in the treatment of ascites is associated with several side effects, including prerenal azotemia, hepatic encephalopathy, and electrolyte and acid-base disorders. A stepped-care approach, together with careful monitoring of patients, is the best way to reduce the incidence of these complications. Ethacrynic acid has been shown to be highly effective in the treatment of ascites, even in patients refractory to other diuretics, but its use is associated with a high incidence of hypokalemia and hypochloremic alkalosis. Bumetanide and piretanide are comparable to furosemide, in terms of both efficacy and side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗

Metabolic effects of temocapril in hypertensive patients with diabetes mellitus type 2.

Compared with other angiotensin-converting enzyme (ACE) inhibitors, the elimination of temocapril is less dependent on renal function. To investigate the metabolic and antihypertensive effects of temocapril in diabetic hypertensives, 30 patients with diabetes mellitus type 2 and mild to moderate hypertension [diastolic blood pressure (BP) 90-115 mm Hg] and without azotemia (plasma creatinine < 180 microM) were evaluated in a prospective randomized double-blind placebo-controlled study. After a 4-week placebo run-in, they received temocapril, 20 mg daily (n = 19), or placebo (n = 11) for 6 weeks. Insulin sensitivity index (SI), determined by the Minimal Model method of Bergman, serum lipoproteins, plasma renin activity, fibrinogen, and microalbuminuria were assessed at the end of the placebo run-in phase and the double-blind treatment phases. Temocapril but not placebo administration produced a significant decrease in supine BP (152/92+/-5/3 vs. 162/98+/-5/2 mm Hg; p < 0.01) and increase in plasma renin (p < 0.05). Variation of SI during temocapril treatment did not reach statistical significance (0.95+/-0.2 before vs. 1.44+/-0.4 x 10(-4)/min/mU/L after treatment). During administration of temocapril or placebo, no significant changes in fasting plasma glucose, insulin, and serum levels of total triglycerides, cholesterol, lipoprotein cholesterol fractions, or fibrinogen were observed. Microalbuminuria decreased significantly on temocapril treatment (49+/-10 vs. 79+/-17 mg/24 h; p < 0.01) but not on placebo. These findings demonstrate that in hypertensive patients with diabetes mellitus type 2, short-term treatment with temocapril is neutral to insulin sensitivity, lipoprotein metabolism, and fibrinogen, and significantly reduces microalbuminuria.

Adult↗

Safety and efficacy of mezlocillin: a single-drug therapy for penetrating abdominal trauma.

This study was done to determine if a single drug, mezlocillin (Mezlo), is as safe and as effective as combined clindamycin (Clind) and gentamicin (Gent) in the treatment of penetrating abdominal wounds. One hundred seventy-three patients received either Mezlo or Clind/Gent combined therapy as assigned by computer-generated randomization. Of these, 147 patients were evaluable. Of 73 patients treated with Clind/Gent the mean duration of hospital stay was 8.9 +/- 4.0 days. Infectious complications developed in 18 patients of whom five failed to respond promptly, but only one required change in therapy. Of 74 patients treated with Mezlo, the mean duration of hospital stay was 9.1 +/- 5.0 days. Infectious complications occurred in 17, in whom four patients failed to eliminate their infections, and two needed changes in antibiotic therapy. None of the patients in either antibiotic group failed because of Enterococcus or Pseudomonas infections. There were no deaths. Twelve isolates of Bacteroides were found in peritoneal fluid cultures and all these patients had colon injuries. The overall therapeutic response was excellent to good in 94% on Clind/Gent and 93% on Mezlo. Azotemia developed in one patient on Clind/Genet and one on Mezlo but no other adverse reactions occurred. The differences shown between the two groups were not statistically significant. We conclude that a single drug mezlocillin is as safe and as effective in the treatment of abdominal trauma as combined clindamycin and gentamicin.

Abdominal Injuries↗

Age-related differences in the metabolic response to injury.

OBJECTIVE: To investigate the effect of age on the metabolic response to injury. METHODS: Fifty-two trauma patients meeting entrance criteria were prospectively enrolled. Patients were grouped by age: elderly, >60 years; and young, < or =60 years. After 4 days of nutrition support, physiologic and laboratory data were collected. Energy and nitrogen metabolism, and body composition were evaluated. RESULTS: Elderly patients demonstrated a reduced incidence of fever (48% vs. 77%,p = 0.027). Independent of body composition, temperature, and injury severity, oxygen consumption was 8% lower in the elderly (p = 0.0032). However, nitrogen loss and myofibrillar catabolic rate was not altered by age. Elderly subjects were more often hyperglycemic (38% vs. 0%, p < 0.0001) and azotemic (62% vs. 22%, p = 0.004), despite similar carbohydrate and protein intake. CONCLUSION: Fever is less common and oxygen consumption lower in elderly trauma patients. Postinjury myofibrillar protein catabolism and nitrogen loss are not influenced by aging. Metabolic complications of nutrition support (hyperglycemia, azotemia) are more common in elderly trauma patients.

Adult↗

The effect of temporary cutaneous diversion on ultimate bladder function.

We evaluated the effect of temporary cutaneous diversion on bladder function in cases of various congenital uropathies. The clinical courses of patients who underwent reversal of vesicostomy or pyelostomy/ureterostomy in a 7-year period were reviewed. Indications for diversion included azotemia, massive hydronephrosis, high grade reflux and/or incomplete bladder emptying. Mean age at diversion was 15 weeks. Overall 75 cases were evaluated (posterior urethral valves in 31, neurogenic bladder in 16, reflux in 14, the syndrome of vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and renal anomalies in 8 and other in 6). Of 55 patients who underwent undiversion by direct closure only 2 required later augmentation for bladder/renal deterioration. Excluding the myelomeningocele patients on clean intermittent catheterization 45 of 46 who underwent direct closure were able to void spontaneously with acceptable post-void residuals. Urodynamics in 22 cases revealed normal bladder capacity at pressures below 30 cm. water in 19 (86%) after direct closure. We conclude that after a period of defunctionalization approximately 75% of children will have essentially normal bladder function. The frequency of bladder augmentation varied from 54% in patients with myelomeningocele to 14% in those with vesicoureteral reflux. This observation suggests that the need for bladder augmentation in the remaining patients is more related to the effect of the primary pathological condition on the detrusor rather than the diversion itself.

Cystostomy↗

Urodynamic risk factors for renal dysfunction in men with obstructive and nonobstructive voiding dysfunction.

PURPOSE: Urodynamic investigation of men with lower urinary tract symptoms, usually attributed to benign prostatic hyperplasia, often reveals bladder outlet obstruction, detrusor instability and/or diminished vesical compliance. We investigated whether these urodynamic abnormalities alone or in combination contribute to renal dysfunction. MATERIALS AND METHODS: A total of 161 men with lower urinary tract symptoms was evaluated by urodynamics, and outlet obstruction, detrusor instability and decreased compliance (30 ml./cm. water or less) were noted. Serum blood urea nitrogen (BUN) and creatinine were measured. Cases were categorized according to the urodynamic diagnosis. Mean values of serum BUN and creatinine as well as the incidence of elevated BUN and creatinine were compared among groups. RESULTS: Of the cohort 54 men (34%) had elevated BUN and 19 (12%) had elevated serum creatinine. No significant correlation was found between the degree of obstruction and BUN or creatinine level. Mean serum BUN and creatinine, and the incidence of abnormal laboratory tests did not significantly differ among those with outlet obstruction, detrusor instability, both conditions or neither condition. However, in patients with outlet obstruction and detrusor instability there was a significantly increased incidence of azotemia in the subgroup with diminished compliance (78%) versus the subgroup with normal compliance (36%). CONCLUSIONS: In men with voiding dysfunction of a nonneurogenic etiology outlet obstruction with or without detrusor instability does not appear to be a risk factor for elevated BUN and creatinine. However, when decreased bladder compliance is associated with a combination of outlet obstruction and detrusor instability, this risk is substantially increased.

Adult↗

The nonneurogenic neurogenic bladder of early infancy.

PURPOSE: The nonneurogenic neurogenic bladder has traditionally been believed to represent a disorder of older children. We report on patients in whom congenital dysfunctional voiding may be the underlying cause of nonneurogenic neurogenic bladder in early infancy. MATERIALS AND METHODS: We evaluated 5 male and 2 female patients newborn to 30 months old with dysfunctional neurogenic bladder and no evidence of neurological pathology or anatomical outflow obstruction. Presentation included prenatal hydronephrosis in 3 cases, urosepsis in 2 and failure to thrive in 2. Radiological and urodynamic investigations revealed thick walled, poorly compliant bladders in 5 patients and incomplete bladder emptying bordering on urinary retention in 2. There was significant upper tract pathology in all cases, including azotemia in 4, reflux in 4 and hydroureteronephrosis in 6. Due to poor bladder function, manifested by incomplete emptying or high storage pressures, all patients were initially treated with cutaneous vesicostomy. RESULTS: Bladder appearance and function subsequently improved in 3 patients and vesicostomy was reversed. Three patients with persistently thickened bladders, including 2 with renal failure, underwent bladder augmentation. The remaining patient had improved bladder storage function but requires intermittent catheterization. CONCLUSIONS: The nonneurogenic neurogenic bladder represents a rare, severe form of dysfunctional voiding that may be present even in the neonatal period.

Child, Preschool↗

Holmium laser enucleation for prostate adenoma greater than 100 gm.: comparison to open prostatectomy.

PURPOSE: Options for treatment of large (greater than 100 gm.) prostatic adenomas have until now been limited to open surgery or transurethral resection by skilled resectionists. Considerable blood loss, morbidity, extended hospital stay and prolonged recovery occur with open surgery for large prostatic adenomas. Endoscopic surgery for benign prostatic hyperplasia has evolved during the last decade to offer the patient and surgeon significant advantages of transurethral removal of prostatic adenomas. Holmium laser enucleation of the prostate with transurethral tissue morcellation provides significant reductions in morbidity, bleeding and hospital stay for patients with large prostate adenomas. MATERIALS AND METHODS: A retrospective review of data on 10 cases of holmium laser enucleation and 10 open prostatectomies for greater than 100 gm. prostatic adenomas was performed from 1998 to 1999 at our institution. Patient demographics, indication for surgery, preoperative and postoperative American Urological Association (AUA) symptom scores, operating time, serum hemoglobin, resected prostatic weight, pathological diagnosis, length of stay and complications were compared. RESULTS: Patient age, indications for surgery (retention, failed medical therapy, high post-void residual, bladder calculi, bladder diverticula and azotemia) and preoperative AUA symptom scores were similar in both groups. Postoperative AUA symptom scores were significantly decreased (p <0.004) in both groups. Operating times were not significantly different. Serum sodium was unchanged by holmium laser enucleation (not significant), and postoperative hemoglobin was not significantly reduced in the holmium laser enucleation group but decreased significantly in the open prostatectomy group (mean decrease 2.9 +/- 0.7 gm., p = 0.0003). Resected weight was greater in the holmium laser enucleation group (151 versus 106 gm., p = 0.07). Length of stay was significantly shorter in the holmium laser enucleation group (2.1 versus 6.1 days, p <0.001). Complications in the holmium laser enucleation group included stress urinary incontinence in 4 cases, prostatic perforation in 1 and urinary retention in 1. No patient treated with holmium laser enucleation was discharged home with an indwelling catheter. Complications in the open prostatectomy group included bladder neck contractures in 2 cases, stress incontinence in 1 and urge incontinence in 1. All patients treated with open prostatectomy were discharged home with an indwelling catheter. CONCLUSIONS: Holmium laser enucleation is an effective, safe procedure for large prostatic adenomas with significantly lower morbidity, catheterization duration and length of stay. Performing holmium laser enucleation for large adenomas requires experience. Stress incontinence was seen frequently with laser but was short-term and self-limited. Holmium laser enucleation is a new procedure, and as experience and expertise increase, it may become an attractive alternative to open prostatectomy for patients with large prostate adenomas.

Aged↗

A randomized comparative trial of three aminoglycosides--comparison of continuous infusions of gentamicin, amikacin and sisomicin combined with carbenicillin in the treatment of infections in neutropenic patients with malignancies.

Continuous infusions of gentamicin, amikacin or sisomicin combined with carbenicillin were compared in a randomized study in the treatment of 572 febrile episodes in 281 patients with cancer. The three treatments (C+A, C+A and C+S) were equally effective with no significant differences in response rate overall (67%, 68%, 67%) or in any infection, except septicemia where C+G had a significantly lower response rate than the other two groups. Pneumonia, the most common infection, had the lowest response rate for all three groups (45-50%). Klebsiella spp. were the most common pathogens and showed a lower response rate than other gram-negative bacilli (P = 0.003). Patients with persistent severe neutropenia had a response rate of 56%. Azotemia was significantly less common in patients with documented infection treated with C+A than in the C+S group. Combinations of carbenicillin plus an aminoglycoside antibiotic are effective for the treatment of infections in neutropenic patients.

Adolescent↗

Crescentic IgA nephropathy.

We report five cases of crescentic IgA nephropathy. All are males, 16-60 years of age. One case each came to medical attention with uremia, nephrotic syndrome, and gross hematuria; two cases presented with microhematuria and proteinuria on routine urinalysis. All had hypertension, azotemia (serum creatinine 1.6-9.4 mg/dl), proteinuria (greater than 6 g/24 hr in four cases), hypoalbuminemia (less than 3 g/dl), and hematuria (gross in two cases). All progressed to end-stage renal failure renal failure ending in dialysis (three cases) or death from unrelated causes (two cases). Prednisone, 60 mg/day for 1 month in two patients (with two 1-g doses of iv methylprednisolone in 1 case) did not improve the serum creatinine level, but one patient subsequently experienced a less rapid fall in renal function. A crescentic glomerulonephritis was present in all biopsies (crescents in 31-80% of glomeruli; mean, 50%). The size and stage of the crescents were variable. Numerous glomeruli had focal or diffuse sclerosis. In all cases, there was a 3 or 4+ deposition of IgA. Low-intensity staining for IgG and IgM was noted in four and three patients, respectively. On electron microscopy, dense granular mesangial deposits were noted in all cases and in four patients capillary subepithelial deposits were also observed. This form of IgA nephropathy is not common, but some studies indicate that it may occur in about 5% of patients with IgA nephropathy.

Adolescent↗

Left-sided endocarditis due to Pseudomonas aeruginosa. A report of 10 cases and review of the literature.

Ten confirmed cases of left-sided endocarditis due to Pseudomonas aeruginosa were reported in detail and the English literature was reviewed. In recent years, venous access (usually illicit) has been the major predisposing factor to this infection and abuse of pentazocine and tripelennamine has been particularly associated with endocarditis due to this organism. This infection involves previously damaged as well as normal valves. The development of congestive heart failure did not adversely affect the prognosis of this infection. However, the development of azotemia was associated with a greater likelihood of a fatal outcome. In the current series, deaths were due to uncontrolled infection. This often occurred despite inhibitory and bactericidal activity in serum generally considered adequate for treatment of endocarditis. Medical treatment alone rarely produced cure of infection. Our experience with a high frequency of major vessel embolization (4/10) and the improved survival after medical/surgical treatment suggests that prompt valve replacement combined with high doses of an aminoglycoside plus carbenicillin or ticarcillin provide the best opportunity for successful outcome in patients with left-sided endocarditis due to P. aeruginosa.

Adult↗

Trichosporonosis in patients with neoplastic disease.

Trichosporonosis due to Trichosporon beigelii or T. capitatum is an infrequent but potentially fatal invasive fungal infection in cancer patients. We studied epidemiologic, clinical, pathologic, and microbiologic features of this infection during a 7-year period at the University of Maryland Cancer Center. Fifteen patients with involvement by Trichosporon were identified: 5 were infected, 5 were possibly infected, and 5 were colonized but not infected by Trichosporon. Four of the infected patients had trichosporonemia and/or positive skin biopsy cultures as the first evidence of infection. The fifth infected patient had positive marrow and skin biopsy cultures. Serial surveillance cultures of infected patients showed preceding Trichosporon colonization in only 1 of 5 cases. Pulmonary infiltrates in 3 infected patients correlated at postmortem examination with Trichosporon pneumonia. Renal dysfunction marked by proteinuria, hematuria, red blood cell casts and azotemia correlated with widespread glomerular infiltration with the fungus. The five infected patients died of their infection, whereas the 2 possibly infected patients who died succumbed to their underlying illness. Trichosporonemia may have been averted in possibly infected patients because of a shorter median duration of profound (less than 100/microliter) neutropenia (5 days) when compared to that of infected patients (20 days). No environmental source of Trichosporon was found in environmental surveillance cultures of food, air, or inanimate surfaces. In vitro studies of three pathogenic strains showed resistance to 5-fluorocytosine but susceptibility to amphotericin B, ketoconazole, and miconazole. Norfloxacin augmented the in-vitro antifungal activity of amphotericin B. Trichosporon must be considered an opportunistic pathogen that can cause serious infections among patients with cancer.

Adolescent↗

Immune complex disease associated with an infected ventriculojugular shunt: a curable form of glomerulonephritis.

A 22-year-old man with a ventriculojugular shunt had edema, hematuria, proteinuria, hypocomplementemia, azotemia, and S epidermidis bacteremia. Initial percutaneous renal biopsy showed a diffuse proliferative glomerulonephritis. Subendothelial and intramembranous deposits were seen on electron microscopy. Immunofluorescent studies were positive for IgG and C3. A repeat percutaneous renal biopsy six weeks after cessation of antibiotic therapy revealed a mild proliferative glomerulonephritis with some evidence of resolution. No deposits were seen on electron microscopy and immunofluorescent studies were negative. At elective shunt revision three months after cessation of therapy, culture of the jugular portion of the removed shunt revealed S epidermidis. Early recognition of immune complex glomerulonephritis occurring with an infected ventriculovascular shunt should permit early treatment (antibiotic therapy and removal of the infected foreign body) and a favorable outcome.

Adult↗

Problems encountered with hyperalimentation in critically ill patients.

An analysis of complications arising from hyperalimentation in 17 septic patients in an ICU is presented. All developed hypophyosphatemia. Hyperglycemia necessitated intravenous insulin in 16 patients. Hypoalbuminemia persisted in all patients despite 134 gm of protein a day. Abnormal liver function and azotemia were common. Catheter complications occurred in three of 90 catheter insertions. Mortality in this population was 70%. Guidelines for the use of Dextrostix for monitoring blood glucose levels and a protocol for hyperalimentation in patients with sepsis are suggested.

Acidosis↗

Conjunctival biopsy in unexplained hypercalcemia.

A 31-year-old woman presented with hypercalcemia, anemia, azotemia, and splenomegaly. Extensive laboratory studies failed to establish the diagnosis, though sarcoidosis seemed likely on the basis of marked hypercalciuria and restrictive lung disease. Conjunctival biopsy showed noncaseating epithelioid granulomas, confirming the clinical diagnosis. Conjunctival biopsy deserves consideration in the evaluation of the patient with unexplained hypercalcemia or other findings suggestive of saroidosis.

Adult↗