Anxiety and depression symptoms in patients with diabetes.

AIMS: To identify the prevalence and major determinants of anxiety and depression symptoms in patients with diabetes. METHODS: A cross-sectional study of 2049 people with Types 1 and 2 diabetes, selected from patients experiencing three different models of care in Ireland: (i) traditional mixed care; (ii) hospital/general practitioner (GP) shared care; (iii) structured GP care. Anxiety and depression symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS). Analyses were conducted primarily using logistic regression with adjustment for relevant confounders. RESULTS: The overall response rate was 71% (n = 1456). Based on the HADS, there was evidence of high levels of anxiety and depression symptoms in patients with diabetes; 32.0% (95% confidence interval = 29.5-34.6%) exceeded the HADS cut-off score of 'mild to severe' anxiety and 22.4% (95% confidence interval = 20.2-24.7%) exceeded the HADS cut-off score of 'mild to severe' depression. Diabetes complications, smoking, uncertainty about glycaemic control and being an ex-drinker or a heavy drinker were risk factors for both higher anxiety and depression scores in multivariate analysis. Female gender and poor glycaemic control were risks factors associated only with higher anxiety scores. Higher socio-economic status and older age were protective factors for lower anxiety and depression scores. Type of diabetes, insulin use, marital status and models of care were not significant predictors of anxiety and depression scores. CONCLUSIONS: The prevalence of anxiety and depression symptoms in patients with diabetes is considerably higher than in general population samples. These data serve as a benchmark for the prevalence of anxiety and depression symptoms in patients with diabetes.

Association of DNA content and proliferative activity with clinical outcome in patients with diffuse mixed cell and large cell non-Hodgkin's lymphoma.

Formalin-fixed and paraffin-embedded lymph node biopsy specimens from 52 untreated patients with newly diagnosed diffuse large cell (n = 48) or mixed cell (n = 4) non-Hodgkin's lymphoma (NHL) were analyzed for DNA content and proliferative activity (PA) by flow cytometry. The results obtained by flow cytometry were compared with the results of cytogenetic studies performed on 28 of the specimens. The median age of the patients was 65 years (range, 15-84 years) and the male to female ratio was 3 to 2. All patients were uniformly staged and uniformly treated with cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The flow cytometric results were compared statistically by univariate analysis with the rate and duration of complete remission and survival. Tumors with low PA (greater than or equal to 80% of cells in G0/G1 phase) were found in 65% of the patients; 74% of those with low PA versus only 44% of those with high PA achieved an initial complete remission (P less than 0.02). DNA aneuploidy was detected in tumors of 56% of the patients and was associated with a significantly longer duration of complete remission (P less than 0.01). Both low PA and aneuploidy independently predicted longer survival. The predicted 2-year actuarial survival for patients with tumors with low PA was 68% versus 10% for those with high PA (P less than 0.01). Similarly, the 2-year survival of patients with aneuploid tumors was 60% versus 36% for those with diploid tumors (P less than 0.01). The combination of PA and DNA content categorized the patients into four groups with decreasing 2-year survivals: low PA/aneuploid (n = 20), 77%; low PA/diploid (n = 14), 57%; high PA/aneuploid (n = 9), 32%; high PA/diploid (n = 9), 0%. The flow cytometric results correlated well with those of the cytogenetic studies. We conclude that low PA and DNA aneuploidy, both separately and in combination, predict a favorable clinical outcome for patients with diffuse mixed cell and large cell NHL.

Exon 7 Ncol restriction site within CYP21B (steroid 21-hydroxylase) is a normal polymorphism.

A point mutation within exon 7 producing an amino acid coding change and a recognition site for the endonuclease Ncol has been reported in the HLA-Bw47-linked CYP21A pseudogene and some mutant CYP21B (steroid 21-hydroxylase) genes of patients with congenital adrenal hyperplasia (CAH). Whether this mutation is deleterious was not demonstrated. We analyzed DNA from various subjects for the presence of the exon 7 Ncol site: group 1, 10 normal subjects; group 2, 11 patients with salt-losing CAH; and group 3, 18 members of an Amish pedigree in which 10 expressed HLA-Bw47 not linked to CAH. Southern blots of Ncol-digested genomic DNA which were hybridized with CYP21 cDNA showed that four subjects of group 1 had a heterozygous Ncol pattern. In group 2, seven patients had the Ncol site; two of them were homozygous for the site and had deletions of both CYP21B genes. The other five were heterozygous for the Ncol site, which was linked to a CYP21B deletion and a HLA-Bw47 haplotype. In group 3, no one exhibited the exon 7 Ncol site. To map the Ncol sites to CYP21A or CYP21B in the normal subjects, DNA from the four Ncol heterozygous subjects was double digested with Ncol and Mbol and hybridized with CYP21 cDNA. Ncol-Mbol fragments unique to CYP21A were identified in all four, but the smaller CYP21B-specific fragments were not detected. Their genomic DNA in the region of exon 7 (bases +1167 to +2058) was then amplified, cloned, and sequenced.(ABSTRACT TRUNCATED AT 250 WORDS)

Low rate of NADPH/ADP-iron dependent lipid peroxidation in hepatic microsomes of DBA/2 mice.

Hepatic microsomal lipid peroxidation has been studied in 4 inbred strains of mice: C57BL/6, BALB/c, AKR and DBA/2. The rates of lipid peroxidation stimulated in vitro by carbon tetrachloride, ascorbate-iron and cumene hydroperoxide were similar in all 4 strains. Lipid peroxidation induced by NADPH/ADP-iron, however, proceeded at a substantially lower rate in the hepatic microsomes of DBA/2 mice. It is suggested that this low rate of enzymic iron-induced lipid peroxidation is a factor that may be involved in the resistance of this strain of mice to experimental hepatic porphyria induced by polyhalogenated aromatic hydrocarbons.

Prostate cancer screening and beliefs about treatment efficacy: a national survey of primary care physicians and urologists.

PURPOSE: To describe practice patterns and beliefs of primary care physicians and urologists regarding early detection and treatment of prostate cancer. SUBJECTS AND METHODS: National probability samples of primary care physicians (n=444) and urologists (n=394) completed mail survey instruments in 1995. Physicians were asked about their use of prostate-specific antigen (PSA) testing for men of different ages and their beliefs about the value of radical prostatectomy, external-beam radiation therapy, and watchful waiting for men with differing life expectancies. RESULTS: Most primary care physicians report doing PSA tests during routine examination of men older than 50 years of age. The majority say they continue to do them on patients over 80 years and to refer men with abnormal values for biopsy. In contrast, only a minority of urologists would recommend PSA tests or biopsy for abnormal values for men over 75 years of age. More than 80% of primary care physicians and urologists doubt the value of radical prostatectomy for men with < 10 years of life expectancy; more primary care physicians than urologists see probable survival benefit in radiation therapy for patients with life expectancy < 10 years (48% versus 36%) or > 10 years (67% versus 53%). Thirteen percent of primary care physicians and only 3% of urologists consider watchful waiting to be as appropriate as aggressive therapy for men with > 10 years of life expectancy. CONCLUSIONS: Primary care physicians are more aggressive about PSA testing and referral for biopsy than most urologists recommend. Both groups recommend PSA testing and believe that aggressive treatment is more beneficial than existing evidence indicates.

A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity.

The oestrogenic and antioestrogenic properties of tamoxifen and its monohydroxylated (monohydroxytamoxifen) and dihydroxylated (dihydroxytamoxifen) metabolites have been investigated in the immature rat. Whether administered orally or subcutaneously, monohydroxytamoxifen was more active than tamoxifen as an antioestrogen. Dihydroxytamoxifen was less active than tamoxifen as an antioestrogen, but this derivative alone was unable to induce a uterotrophic response. Both metabolites of tamoxifen were potent inhibitors of the binding of [3H]oestradiol to oestrogen receptors in vitro. It is possible that the metabolites play a supportive role in the antioestrogenic activity of tamoxifen. The potent activity of monohydroxytamoxifen in vivo and in vitro suggests that this compound could be an important new tool for the subcellular investigation of oestrogenic and antioestrogenic events.

Linkage of congenital isolated adrenocorticotropic hormone deficiency to the corticotropin releasing hormone locus using simple sequence repeat polymorphisms.

Genetic screening techniques using simple sequence repeat polymorphisms were applied to investigate the molecular nature of congenital isolated adrenocorticotropic hormone (ACTH) deficiency. We hypothesize that this rare cause of hypocortisolism shared by a brother and sister with two unaffected sibs and unaffected parents is inherited as an autosomal recessive single gene mutation. Genes involved in the hypothalamic-pituitary axis controlling cortisol sufficiency were investigated for a causal role in this disorder. Southern blotting showed no detectable mutations of the gene encoding pro-opiomelanocortin (POMC), the ACTH precursor. Other candidate genes subsequently considered were those encoding neuroendocrine convertase-1, and neuroendocrine convertase-2 (NEC-1, NEC-2), and corticotropin releasing hormone (CRH). Tests for linkage were performed using polymorphic di- and tetranucleotide simple sequence repeat markers flanking the reported map locations for POMC, NEC-1, NEC-2, and CRH. The chromosomal haplotypes determined by the markers flanking the loci for POMC, NEC-1, and NEC-2 were not compatible with linkage. However, 22 individual markers defining the chromosomal haplotypes flanking CRH were compatible with linkage of the disorder to the immediate area of this gene on chromosome 8. Based on these data, we hypothesize that the ACTH deficiency in this family is due to an abnormality of CRH gene structure or expression. These results illustrate the useful application of high density genetic maps constructed with simple sequence repeat markers for inclusion/exclusion studies of candidate genes in even very small nuclear families segregating for unusual phenotypes.

Risk factors for clinical benign prostatic hyperplasia in a community-based population of healthy aging men.

We defined risk factors for a clinical diagnosis of benign prostatic hyperplasia (BPH) among subjects of the population-based Massachusetts Male Aging Study. In 1987-89 1709 men aged 40-70 provided baseline risk factor data and were followed for a mean of 9 years; 1019 men without prostate cancer provided follow-up data. We classified men with clinical BPH at follow-up if they reported (1) frequent or difficulty urinating and were told by a health professional that they had an enlarged or swollen prostate or (2) if they reported having surgery for BPH. At follow-up the prevalence of clinical BPH was 19.4%, increasing from 8.4% of men aged 38-49 years to 33.5% of men aged 60-70 years (P < 0.001 for trend). Elevated free PSA levels (age- and total PSA-adjusted OR, top vs. bottom quartile ng/mL 4.4, 95% CI 1.9-10.5), heart disease (age-adjusted OR 2.1, CI 1.3-3.3), and use of beta-blocker medications (OR 1.8, CI 1.1-3.0) increased odds for BPH, while current cigarette smoking (OR 0.5, CI 0.3-0.8) and high levels of physical activity (top vs. bottom quartile kcals/day OR 0.5, CI 0.3-0.9) decreased odds of BPH. All but the medication effects persisted in fully adjusted multivariable models. Total or fat calorie intake, sexual activity level, alcohol intake, body mass index, waist-hip ratio, diastolic blood pressure, a history of diabetes, hypertension, vasectomy, or serum levels of androgens or estrogens did not individually predict clinical BPH. We conclude that physical exercise and cigarette smoking appear to protect against development of clinical BPH. Elevated free PSA levels predict clinical BPH independent of total PSA levels. Risk associated with heart disease does not appear to be due solely to detection bias or to effects of heart disease medications. A wide variety of other characteristics appear to have no influence on risk for clinical BPH.

Prevalence of bothersome genitourinary symptoms and diagnoses in younger men on routine primary care visits.

OBJECTIVES: To assess the prevalence of bothersome genitourinary (GU) symptoms in younger men on routine primary care physician visits. METHODS: One hundred six men aged 18 to 50 years were approached to complete a brief, self-administered survey that included the American Urological Association Symptom Index, a benign prostatic hyperplasia (BPH) Impact Index, and additional questions about GU pain and sexual dysfunction and about a history of GU diseases. Men with GU symptoms had their outpatient records reviewed. RESULTS: Of the 101 respondents (mean age 36 years), 50% reported GU symptoms. Of these men, 25% were bothered by their symptoms and 17% wanted to talk about them with their physicians; 22% were worried that their GU symptoms might be due to prostate cancer; 27% of all men reported a history of at least one GU disease and 17% had more than one; 16% of all men had been to a urologist. Chart review for the 51 men with symptoms revealed physician documentation of GU symptoms in only 24% of cases and an abnormal GU examination in 8%. One third of reviewed charts documented a GU problem that visit. A broad spectrum of GU diagnoses was documented; no one cause predominated. Ninety percent of all men reported that primary care physicians should routinely ask younger men GU questions as part of their general healthcare. CONCLUSIONS: The high prevalence of bothersome GU symptoms and diagnoses in younger men suggests that information about the clinical, functional, and quality of life implications of these symptoms needs to be collected in this population.

Distinguishing chronic prostatitis and benign prostatic hyperplasia symptoms: results of a national survey of physician visits.

OBJECTIVES: The morbidity of chronic prostatitis results from a constellation of genitourinary symptoms. A recent study classified 21 of these symptoms into three categories: pain, voiding complaints, and sexual dysfunction. Pain symptoms predominated among patients with prostatitis. Using data from a nationwide survey of physician visits, we examined the most common symptoms reported by men at chronic prostatitis visits and contrasted the results with visits for benign prostatic hyperplasia (BPH). METHODS: We analyzed 81,034 visits by men (18 years and older) to office-based physicians of all specialties in the National Ambulatory Medical Care Surveys of 1990 to 1996, using sampling weights to make national estimates. U.S. physicians selected by random stratified sampling completed visit forms that included patients' reasons for visits and physicians' diagnoses. RESULTS: In 1990 to 1996, there were 765 visits (national estimate 1.5 million visits/yr; 95% confidence interval = 0.9 to 2.1) with a diagnosis of chronic prostatitis. Among chronic prostatitis visits, 20% were for pain, 19% for urinary symptoms, and 1% for sexual dysfunction. Among 2271 BPH visits, 2% were for pain, 33% for voiding complaints, and 1% for sexual dysfunction. The most common reason coded for chronic prostatitis visits was painful urination (14% of chronic prostatitis visits, but only 1.7% of BPH visits). CONCLUSIONS: Pain was slightly more common than voiding complaints, but much more common than sexual dysfunction among chronic prostatitis visits. The most common reason for chronic prostatitis visits was painful urination, which was uncommon among patients with BPH. Pain distinguished chronic prostatitis from BPH better than any other urinary symptom.

Faculty training in general internal medicine: a survey of graduates from a research-intensive fellowship program.

PURPOSE: To determine the fellowship experiences and career activities of the graduates of a research-intensive general internal medicine fellowship program. METHOD: In 1997, the authors surveyed all graduates of the Harvard General Internal Medicine Fellowship Program, a research-intensive fellowship begun in 1979. RESULTS: Of 105 surveys delivered to graduates, 103 (98%) were returned. During the fellowship, 82 graduates (80%) presented research findings at regional or national meetings, 89 (86%) published peer-reviewed articles based on their fellowship work, 75 (73%) precepted residents or medical students in the ambulatory setting, and 67 (65%) taught medical students in the preclinical years. At the time of the survey, 100 graduates (97%) held academic appointments: 48 as clinician-investigators, 23 as clinician-administrators, 15 as clinician-educators, and 15 as clinicians. CONCLUSION: Graduates of this research-intensive fellowship pursued academic careers with research, teaching, administration, and clinical activities. Directors of similar fellowship programs should prepare their graduates for all these activities.

Ultrasound scattering from spherical tumours.

The interaction of biomedical ultrasound with spherical tumours in the human body is investigated using analytic methods which predict the angular distribution of the ultrasound scattered by the tumour. Both the tumour and the surrounding tissue are considered to be lossy elastic media, which support shear-wave modes in addition to the familiar compressional-wave acoustic modes. Exact expressions for the angular distribution of the ultrasonic energy scattered by the tumour are used to illustrate graphically the behaviour of plane ultrasound wave interactions.

Morphological assessment of the soft palate in habitual snoring using image analysis.

OBJECTIVES: Define differences in palatal and uvular dimensions between habitual snorers and healthy nonsnoring control subjects. Document the changes in palatal configuration after different types of palatoplasty. STUDY DESIGN: A prospective controlled clinical study was performed analyzing video recordings of the soft palate and oropharynx of 251 subjects (121 habitual snorers, 79 patients after laser-assisted uvulopalatoplasty ([LAUP], and 51 healthy volunteers). METHODS: The recordings were captured using a rigid endoscope with a reference measure applied to the soft palate and a mark at the junction of the soft and hard palate. Four parameters were studied in the captured pictures after correction for the distortion deformity in fiberoptic endoscopic images: 1) length of soft palate, 2) length of uvula, 3) width of uvula, and 4) distance between posterior pillars. RESULTS: Analysis showed that habitual snorers, compared with healthy volunteers have significantly increased soft palate length (P = .00001), increased uvula length (P = .0002) and width (P = .00001), and narrowed oropharyngeal isthmus (distance between the posterior pillars) (P = .04). In patients studied after LAUP, the length of the soft palate is significantly shorter (P = .00001) than in the preoperative cohort, and the oropharyngeal isthmus is significantly narrower (P = .00001). Moreover, this latter distance is significantly narrower (P = .00001) when compared with healthy volunteers. CONCLUSIONS: Habitual snorers have a long soft palate, a long wide uvula, and a narrowed oropharyngeal isthmus. LAUP shortens and tightens the elongated palate and causes a further reduction in the space between the posterior pillars.

Medical malpractice implications of PSA testing for early detection of prostate cancer.

Prostate cancer screening is controversial. We conducted a national survey of primary care physicians and urologists to examine their use of prostate-specific antigen testing and their views on medical liability issues involved.

Nutritional consequences of radiotherapy in early laryngeal carcinoma.

In treating patients with malignant head and neck disease, radiotherapy may compromise their oral intake and, thus, their nutritional status. This study aimed to assess a subgroup of patients who received small field radiotherapy, where their early primary tumour itself would not be expected to affect swallowing and where significant nutritional problems are not traditionally identified. A retrospective analysis of hospital records was undertaken on 61 patients, treated for T1 and T2 N0 laryngeal squamous cell carcinoma with primary radical radiotherapy over a three year period (1993-1995 inclusive). At presentation, 97% had their weight and height recorded, enabling calculation of their body mass index (BMI); 13% presented with a BMI < 20 kg/m2 and the 26% of patients who complained of weight loss at presentation had a mean percentage weight loss of 5.35%. During treatment, 79% of patients had their weight recorded and 49% had a documented mean percentage weight loss of 6.4%. The mean BMI at the end of treatment was significantly lower than at presentation (P = 0.03). These effects occurred despite 80% of patients having at least one dietetic consultation (mean 3.5 consults), and 75% having received high protein/high calorie supplementation. The percentage weight loss during treatment correlated significantly with the gamma-glutamyl transpeptidase (gamma-GT) level at presentation. The biochemical markers, haemoglobin and albumin, were normal in the great majority at presentation and fell non-specifically during treatment in 82% and 56% of patients, respectively. We conclude that significant numbers of patients with early laryngeal malignancy are undernourished at presentation and, despite dietetic support, endure considerable nutritional problems during radiotherapy. Attention to nutritional issues is mandatory even in this group of patients previously considered to be less at risk because of the site and early stage of their disease.

Posterior tracheal wall diverticula-an unexpected finding.

Two cases of asymptomatic posterior tracheal wall diverticula, one single and one multiple, found unexpectedly at laryngectomy are described. The embryonal development and pathogenesis of tracheal abnormalities are discussed, and possible clinical implications speculated upon.

Cochlear implantation in a district general hospital: problems and complications in the first five years.

Fifty-three patients, 34 adults and 19 children have been implanted over the first five years of the cochlear implant programmed at the North Riding Infirmary (NRI). For a small centre, based at a district general hospital, our complication rate compare favourably with others: 11.7 per cent adult and 10.5 per cent paediatric major complications. Data on all patients was gathered prospectively as part of the national cochlear implant programme, and we report and discuss all complications from this centre.

Parapharyngeal lipoma.

Lipomas of the parapharyngeal space provide both a diagnostic and therapeutic challenge. They are extremely rare with only a few cases having been reported. We present the case of a right parapharyngeal space lipoma in a 69-year-old man that was excised via a transcervical approach.