Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study.

BACKGROUND: Identifying patients at risk of developing diabetic peripheral neuropathy (DPN) is of paramount importance in those with type 2 diabetes mellitus (T2DM) to provide and anticipate secondary prevention measures as well as intensify action on risk factors, particularly so in primary care. Noteworthy, the incidence of DPN remains unknown in our environment. AIMS: (i) To analyze a single angiotensin-converting enzyme (ACE) gene polymorphism (D/I) as a genetic marker of risk of developing DPN, and (ii) to determine the incidence of DPN in our environment. RESEARCH DESIGN AND METHODS: Longitudinal study with annual follow-up for 3years involving a group of T2DM (N=283) randomly selected. ACE gene polymorphism distribution (I=insertion; D=deletion) was determined. DPN was diagnosed using clinical and neurophysiology evaluation. RESULTS: Baseline DPN prevalence was 28.97% (95% CI, 23.65-34.20). ACE polymorphism heterozygous genotype D/I presence was 60.77% (95% CI, 55.05-66.5) and was independently associated with a decreased risk of DPN (RR, 0.51; 95% CI, 0.30-0.86). DPN correlated with age (P<0.001) but not with gender (P=0.466) or time of evolution of T2DM (P=0.555). Regarding end point, DPN prevalence was 36.4% (95% CI, 30.76-42.04), and accumulated incidence was 10.4% 3years thereafter. In the final Poisson regression analysis, the presence of heterozygous genotype remained independently associated with a decreased risk of DPN (RR, 0.71; (95% CI, 0.53-0.96). DPN presence remained correlated with age (P=0.002), but not with gender (P=0.490) or time of evolution (P=0.630). CONCLUSIONS: In our series, heterozygous ACE polymorphism (D/I) stands as a protective factor for DPN development. Accumulated incidence of DPN was relevant. Further prospective studies are warranted.

Clinical screening and diagnosis of diabetic polyneuropathy: the North Catalonia Diabetes Study.

BACKGROUND: To evaluate the prevalence of diabetic polyneuropathy (DPN) and develop a simple and accurate method for the evaluation of DPN risk in primary care settings. MATERIALS AND METHODS: Cross-sectional descriptive study in a random sample (N = 307) of type 2 diabetes mellitus participants. DPN was diagnosed by both clinical neurological examination and simplified DPN Selection Method in each patient. Correlation between the two methods was obtained. RESULTS: Prevalence of DPN was 23.13% (confidence interval,18.38-27.87) according to clinical neurological examination. Noteworthy, clinical neurological evaluation scores were related to nerve conduction studies (r = 0.882; P < 0.0005). DPN presence was positively related to age, metabolic control (HbA1c levels), known duration of diabetes, diabetic retinopathy, cardiovascular disease, peripheral ischemia and systolic and diastolic blood pressure, but was negatively related to current high-density lipoprotein cholesterol (HDL-C) levels (P < 0.0001). The sensitivity and specificity of our DPN Selection Method (using four clinical parameters: age, retinopathy, HbA1c and HDL-C plasma levels) for diagnosis of DPN was 74.20% and 74.90%, respectively. CONCLUSIONS: The expected prevalence of DPN was observed. The sensitivity of the DPN Selection Method correlated well with formal clinical neurological exam in detection of the condition. We therefore conclude the DPN Selection Method is a useful tool in primary care settings in the evaluation and diagnosis of DPN.

Hydrocephalus in coccidioidal meningitis: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Coccidioidomycosis was once confined to the southwest United States and northern Mexico. It has become a larger concern because of the concentration of military bases in these areas, the increasing mobility of populations, and the rising population of immunocompromised persons. Outside endemic areas, the diagnosis is rarely considered. Patients with coccidioidomycosis may develop occult basilar meningitis progressing to communicating hydrocephalus and death. CLINICAL PRESENTATION: A 60-year-old white man presented with a 1-month history of vertigo, falls, and vomiting. Computed tomography of the head revealed mild hydrocephalus. Lumbar puncture results were remarkable for 1065 mg/dl protein; acid-fast bacillus stain, Gram's stain, and culture results were negative. Postgadolinium magnetic resonance imaging demonstrated enhancement of basilar and cervical meninges, suggesting inflammation, and communicating hydrocephalus. For 48 hours, the patient's level of consciousness decreased progressively. INTERVENTION: A ventriculoperitoneal shunt was placed, and antifungal agents were initiated on an emergent basis. CONCLUSION: Coccidioidomycosis should be considered in the differential diagnosis of occult basilar meningitis. The diagnosis is established by the discovery of a high (>1:2) titer of complement-fixing antibody in the cerebrospinal fluid. Communicating hydrocephalus is a common complication of untreated coccidioidal meningitis, and it may develop during appropriate treatment (oral fluconazole, 200-400 mg/d, continued indefinitely). Patients with hydrocephalus and evidence of increased intracranial pressure require a shunt.

Sexual function in men with diabetes type 2: association with glycemic control.

PURPOSE: We evaluated the association of glycemic control with erectile dysfunction in men with diabetes type 2. MATERIALS AND METHODS: A convenience sample of men with diabetes type 2 at the Cleveland Veterans Affairs Medical Center completed questions 1 to 5 of the International Index of Erectile Function. The primary outcome measure was erectile function score, calculated as the sum of questions 1 to 5. Details of disease duration, complications, medication use, patient age and level of glycosylated hemoglobin were obtained by reviewing the medical record. RESULTS: Mean subject age plus or minus standard deviation was 62.0+/-12.3 years, mean hemoglobin A1c was 8.1%+/-1.9% and mean erectile function score was 16.6+/-5.9 (range 5 to 23). Stratified analysis revealed that mean erectile function score decreased as hemoglobin A1c increased (analysis of variance p = 0.002). The test for linearity was also significant (p = 0.001). There were no statistically significant associations of levels of glycemic control with alpha-blocker, beta-blocker or diuretic use. Bivariate analysis showed a significant correlation of hemoglobin A1c with neuropathy but not with patient age, duration of diabetes, alpha-blockers, beta-blockers or diuretics. Multivariate analysis demonstrated that hemoglobin A1c was an independent predictor of erectile function score (p<0.001) even after adjusting for peripheral neuropathy, which was also an independent predictor (p = 0.023). CONCLUSIONS: Our data add to the growing body of literature suggesting that erectile dysfunction correlates with the level of glycemic control. Peripheral neuropathy and hemoglobin A1c but not patient age were independent predictors of erectile dysfunction.

Comprehensive versus holistic care. Case studies of chronic disease.

Persons with chronic disease often experience an involvement of multiple body systems. A comprehensive care approach to patient care is often used with the belief that a health care team will ensure that a patient's needs will be covered. Instead, this approach is reductionist in practice and leads to fragmentation of care, and the difficult patients often slip through the cracks of the health care system. However, a holistic theory-based approach puts a patient's perceived needs first and offers care not only for the body but also for the human spirit. Two case studies of patients with chronic disease are reviewed, both of whom began in a comprehensive care model and ended up with holistic care. Suggestions for assisting in the movement of a comprehensive care model toward a holistic model are offered for the practicing nurse.

Incidental pituitary macroadenoma: a population-based study.

Epidemiologic analysis of incidental macroadenoma is limited to autopsy studies and case series. There are no published data about prevalence of incidental pituitary macroadenoma in living patients. The objective of this study was to determine the prevalence of incidental pituitary macroadenoma. It was designed as an observational study of cranial computed tomography reports. An urban department of veterans affairs medical center was used for the setting. The subject group consisted of 3,550 consecutive patients at the Cleveland Department of Veterans Affairs Medical Center from January 1993 to January 1996. Patients with known or suspected pituitary or parasellar disease were excluded. Cranial computed tomography reports were reviewed. Original films and medical charts of all patients with pituitary macroadenoma were reviewed. Seven patients with incidentally discovered pituitary macroadenoma that ranged from 1 cm to 2.5 cm were found; prevalence was 0.20% (95% confidence interval 0.05, 0.35%). Evidence of partial hypopituitarism was found in most patients. All patients had normal visual fields at initial examination despite the size of the tumor, but 1 of 4 had a field cut demonstrated by Goldmann perimetry. These data confirm that, although the prevalence of incidental pituitary macroadenoma is low, screening identified patients to detect deficiency of corticotropin, thyroid-stimulating hormone, and gonadotropins and to detect visual field defects is important.

Hyperfunction and hypofunction in the anterior pituitary.

The actions and interactions of the pituitary gland and the nervous system constitute a regulatory system whereby the physiologic activity of the thyroid, adrenals, and gonads is controlled. Damage to or interference with the pituitary gland may cause hyper- or hypofunctional states resulting in devastating changes in a person's body and life. This article limits its discussion to several of the more frequently encountered pathological states, their diagnostic work-up, evaluation, and treatment.

Osteoporosis in men: a review.

Osteoporosis has been extensively written about, yet the majority of articles deal only with the population of women patients. This article broadens the scope of the problem to include men, in whom osteoporosis is more common than has been realized. A significant percentage of men are at risk of developing, or have developed, osteoporosis, but unfortunately screening for osteoporosis is often not included in routine examinations. It is particularly a problem of older men. As testosterone begins to decrease with age, risk of osteoporosis dramatically increases as it does in postmenopausal women. This article will review basic risk factors pertaining to men, diagnostic approaches, and treatment strategies.

Hyperprolactinaemia and verapamil: prevalence and potential association with hypogonadism in men.

OBJECTIVE: Verapamil has been associated with hyperprolactinaemia, but there have been no population-based studies. Our objective was to determine the prevalence and degree of hyperprolactinaemia associated with verapamil in the clinical setting. DESIGN: Observation with cross-sectional and longitudinal components in the setting of an urban teaching hospital and its satellite out-patient clinics. PATIENTS: Male out-patients excluding those taking other drugs known to raise PRL, renal failure and known primary hypothyroidism (1265 eligible subjects). Control subjects were drawn from eligible out-patients not taking verapamil. MEASUREMENTS: Serum PRL levels, frequency of persistent hyperprolactinaemia and total testosterone levels. RESULTS: Prolactin levels were obtained in 449 subjects on verapamil (35.5% response rate) and 166 controls. The proportions of individuals with hyperprolactinaemia (PRL > 460 mU/l) were 0.085 and 0.030 in the verapamil and control groups, respectively (P = 0.012, X2-test). The mean (+/- SD) serum PRL levels were 267 +/- 205 and 203 +/- 118 mU/l in the verapamil and control groups, respectively (P < 0.001, independent t-test). Of the 38 patients with previously determined elevated PRL levels, follow-up data were obtained in 25 (65.8%); one was found to have a pituitary adenoma and was excluded from the analysis. Fifteen of the 24 were still on verapamil (Group 1) and 14 (93.3%) continued to be hyperprolactinaemic. In 9 patients verapamil had been discontinued (Group 2) and all had normal PRL levels. Continued verapamil use was associated with persistent hyperprolactinaemia (odds ratio > 120, P < 0.00001). The mean +/- SD serum testosterone levels at follow-up were significantly lower in Group 1 (6.16 +/- 2.52 nmol/l) than in Group 2 (9.42 +/- 3.92 nmol/l, P = 0.029, independent t-test). CONCLUSIONS: The prevalence of hyperprolactinaemia associated with verapamil use in this study of male out-patients was 8.5% (95% CI 5.9-11.1%). The persistence of hyperprolactinaemia when verapamil was continued (Group 1) and the return to normal PRL levels when verapamil was discontinued (Group 2) confirm verapamil's causal role in the development of hyperprolactinaemia. While low testosterone levels were common in both groups, testosterone levels were lower in patients on verapamil. Our data suggest that screening for hyperprolactinaemia should be considered in male patients taking verapamil.

Verapamil-induced hyperprolactinemia complicated by a pituitary incidentaloma.

OBJECTIVE: To describe a patient with an incidental pituitary lesion who experienced verapamil-induced hyperprolactinemia. CASE SUMMARY: A patient experiencing impotence was found to have increased prolactin and low testosterone concentrations. Verapamil as a cause for his increased prolactin concentration was not considered initially. The patient underwent extensive testing to rule out a pituitary tumor. Magnetic resonance imaging showed a 6-mm lesion consistent with a pituitary microadenoma that had remained unchanged for 6 months. Verapamil therapy was discontinued and within 1 month the patient's prolactin concentration decreased from 46.8 to 14.4 micrograms/L, and has remained within normal limits. DISCUSSION: We reviewed reports of verapamil-induced hyperprolactinemia. This case was unique as this patient had an incidental pituitary lesion that was not responsible for increasing the prolactin concentration in our patient, but rather complicated the identification of a drug-induced disorder. CONCLUSION: The failure to identify the hyperprolactinemic effect of verapamil may have resulted in performing unnecessary radiologic procedures in this patient. This case highlights the importance of obtaining a medication history in patients with hyperprolactinemia.

Interdisciplinary integration for quality improvement: the Cleveland Veterans Affairs Medical Center Firm System.

BACKGROUND: Many of the characteristics of Firm Systems lend themselves to the application of principles of continuous quality improvement (CQI). A Firm System is defined as two or more parallel practices organized on the principle of continuity of relationships between patients and an interdisciplinary group of health care professionals and trainees. Firm Systems are organized around the care of the patient or customer and emphasize access, continuity, and quality of care. CASE STUDY: The Firm System was implemented at the Cleveland Veterans Affairs Medical Center (VAMC) not as a CQI initiative per se, but as an effort to coordinate the processes involved in the delivery of patient care. The primary goals of this implementation were to improve the quality of patient care, medical education, and health care research. The main strategy to deal with problems caused by uncoordinated care were to move from a departmental approach to an integrated interdisciplinary approach. This approach represented a paradigm shift within the organization that extended to planning, documentation, and the general work environment. Most important, the institution had leaders who were committed to the Firm System and willing to authorize resources to ensure its success. CONCLUSION: VA hospitals are ideal settings for Firm Systems because they provide longitudinal, comprehensive care with a centralized, prepaid payment mechanism, and they have well-developed information systems that allow the random assignment of patients to Firms. Recommendations to others interested in implementing Firm Systems include creation of a written plan that can gain general support; identification of resources needed for successful implementation; remembering that the patient is the most important customer, as well as that complex systems have many customers; monitoring of performance; and the importance of randomizing patients and providers.