Measurement errors in epidemiological studies of human papillomavirus and cervical cancer.

Measurement errors have been an important concern in studies of human papillomavirus (HPV) and anogenital cancers. Misclassification of HPV infection status is a possible explanation for incoherent findings in previous epidemiological studies purporting to show an etiological role for HPV in cervical cancer. Even low levels of misclassification of HPV infection can cause severe underestimation of HPV prevalence in field surveys, bias the association between HPV and sexual activity, and impair the ability to control statistically the relation between sexual activity and neoplasia by viral status. The present report focuses on aspects that have not been elaborated in two previous studies (Kaldor, 1989; Franco, 1991). Emphasis is given to effects of measurement errors of HPV infection status in biasing the association with cervical neoplasia under more complex scenarios, e.g., differential misclassification between cases and controls in a case-control study, and non-differential misclassification of both viral infection and cervical neoplasia in cross-sectional cytology surveys and cohort studies. Some simple numeric formulae are given that allow the correction of prevalence rates and epidemiological measures of effect, such as the odds ratio and the relative risk, under the latter conditions of misclassification constraint. These formulae have been used to correct estimates from recent epidemiological studies using hypothetical misclassification scenarios in order to obtain clues on the magnitude of the underlying relationship between HPV and cervical cancer.     

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Quality of case management of sexually transmitted diseases: comparison of the methods for assessing the performance of providers.

This article examines the reliability and validity of direct observation of patient-provider encounters, interviews with providers, and use of patients simulating sexually transmitted diseases (STD) as methods for assessing the quality of STD case management in developing countries. Data were collected during an STD health facility survey in Malawi; the performance of 49 providers was observed, and the providers were also interviewed; 20 of them were visited by a simulated patient complaining of urethral discharge. Agreement (based on the kappa statistic) was generally poor between direct observation and provider-interview data, and also between direct observation and simulated-patient data. In contrast, percentage agreements between direct observation and simulated-patient data were often high. Multiple observations on providers indicated that a provider''s behaviour is not consistent across several patients. Simulated-patient data are probably the best in reflecting normal performance, but their feasibility for routine quality assessment is limited because the provider''s behaviour is not consistent and would require multiple data points. Direct observation data are the best option for assessing quality if the results are assumed to reflect better than normal levels of quality of care. Data from interviews with providers should be viewed with caution, because they may reflect provider knowledge and not necessarily performance.     

Revisiting the prognostic role of gallium scintigraphy in low-grade Non-Hodgkin’s lymphoma

The purpose of this study was threefold: to evaluate the role of gallium-67 scintigraphy in the staging of low-grade non-Hodgkin’s lymphomas (LGNHL), to assess the relationship between the expression of CD71 on the surface of the neoplastic cells and the ⁶⁷Ga uptake by the tumour, and to establish the contribution of ⁶⁷Ga scan in defining the prognosis of LGNHL. Forty-eight patients with untreated LGNHL diagnosed in a single institution over a decade were reviewed. The end point of the study was survival of the patients according to the scintigraphic ⁶⁷Ga score at diagnosis. In addition to ⁶⁷Ga scan, other prognostic variables were studied, relating to the neoplastic burden, the biology of the tumour and the host. Univariate and multivariate analyses were used. ⁶⁷Ga scan identified only 116/286 (41%) nodes involved by lymphoma that were detected by clinical examination or computed tomography scan. A scintigraphic scoring system with an arbitrary cut-off value of 3 (high scan score) was able to predict patients with a dismal prognosis: with a mean follow-up of 47 months (range: 1–146 months) the median survival time was 28 months in patients with a high scan score and 74 months in patients with a low scan score (P=0.002). CD71 values were 27.4%±14.9% (mean ±SD) in the former and 8.9%±7.2% in the latter (P=0.0001). Only performance status and extranodal sites were significant variables for prognosis in multivariate analysis. It is concluded that ⁶⁷Ga scan is inaccurate in staging but might be very important in defining the prognosis in LGNHL, in association with other prognostic variables. Received 1 May and in revised form 6 August 1997     

The afferent innervation of the thymus gland in the rat

The afferent nervous supply to the thymus gland has been investigated by means of the retrograde transport of horseradish peroxidase. It has been shown that the thymus receives an afferent supply from the nodose ganglia of the vagus and from the dorsal root ganglia C₁–C₇. The afferent innervation of the right and left thymic lobes is bilaterally organized; the fibers of a small celled population of nodose ganglion neurons cross outside the thymus and those of a larger celled population cross within the thymus gland. The functional implications of these findings are discussed in the context of central nervous system-immune system interactions.     

Segmentectomies in the management of liver tumors

Between 1982 and 1986, liver segmentectomies were performed in 19 patients with liver tumors, including ten hepatocellular carcinomas, six liver metastases, one cholangiocarcinoma, and two benign tumors. During surgery, patients received a mean (+/- 1 SD) of 1050 +/- 150 mL of packed red blood cells and 860 +/- 80 mL of fresh-frozen plasma. There were no operative deaths. The only complication was a prolonged leakage of ascites through the abdominal drain in one patient with cirrhosis. Seven patients with hepatocellular carcinoma were still alive at this writing, with a follow-up ranging from two months to four years. The four patients with metastases from colorectal carcinomas were alive after follow-up times ranging from six to 24 months. These results suggest that liver segmentectomy is a safe procedure and should be considered as the operation of choice for resection of limited liver tumors.     

Endothelial Vascular Function in Hypertensive Patients After Renin—Angiotensin System Blockad

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%±2.4% vs 13.5%±2.0%; hydrochlorothiazide, 7.3%±2.0% vs 12.8%±3.1%; QUIN, 7.2%±2.8% vs 13.2%±2.1%; IRBE, 7.1%±2.8% vs 13.0%±2.9%; and IRBE + QUIN, 7.5%±1.9% vs 12.8%±3.0%. Nitroglycerin-mediated responses were: normal, 26.0%±1.9% vs 24.0%±2.5%; hydrochlorothiazide, 17.0%±2.2% vs 18.3%±2.6%; QUIN, 17.8%±3.2% vs 23.4%±3.0%; IRBE, 16.8%±3.6% vs 24.7%±2.0%; and IRBE + QUIN, 17.3%±3.0% vs 25.1%±2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

Using clinical signs to diagnose anaemia in African children.

Anaemia is a serious and common problem among young children in sub-Saharan Africa. As a first step towards developing guidelines for its recognition and treatment, we conducted a study to evaluate the ability of health workers to use clinical findings to identify children with anaemia. Health care workers examined a total of 1104 children under 5 years of age at two hospital-based outpatient clinics in rural Malawi. Blood samples were taken to determine haemoglobin concentrations. Pallor of the conjunctiva, tongue, palm or nail beds was 66% sensitive and 68% specific in distinguishing children with moderate a anaemia (haemoglobin concentration, 5-8 g/dl) and 93% sensitive and 57% specific in distinguishing those with severe anaemia (haemoglobin concentration, < 5 g/dl). Even without laboratory support, which is often unavailable in rural Africa, clinical findings can identify the majority of children with anaemia.     

Monocular contribution to the peak time of the binocular pattern visual evoked potential

The contribution of each monocular pathway to the timing of the binocular pattern visual evoked potential was assessed in situations where a significant interocular timing discrepancy was observed. Monocular and binocular pattern visual evoked potentials to 0.5° checks were recorded from normal subjects, normal subjects in whom one eye was blurred, patients with monocular amblyopia, and patients with resolved unilateral optic neuritis. Normal subjects showed facilitation, while suppression was evidenced in subjects with monocular blurring. In patients with amblyopia, the affected pathway had no effect on binocular pattern visual evoked potential latency, suggesting that the amblyopic eye was suppressed. In contrast, all patients with optic neuritis showed binocular averaging. Our results show that different forms of binocular interaction are evidenced in normal subjects, in amblyopia and in optic neuritis, and suggest that a comparative analysis of monocular and binocular pattern visual evoked potential peak times brings valuable information to the clinical evaluation that could be used to distinguish disease processes further.Abbreviation BPVEP binocular pattern visual evoked potential     

Immunohistological study of grumose degeneration of the dentate nucleus in progressive supranuclear palsy

The grumose degeneration observed in the dentate nuclei of 7 cases of progressive supranuclear palsy (PSP) was studied with a panel of antibodies which included 2 neurofilaments, Tau and ubiquitin. Dentate nucleus neurons were negative with all antibodies except ubiquitin which showed a slightly positive homogeneous pattern of staining. The amorphous material surrounding swollen or normal neurons was strongly positive for neurofilament and subunits and numerous torpedoes were observed in the granular layer of the cerebellar cortex. Our results confirm that grumose degeneration consists in degeneration of terminal axons of Purkinje cells in the dentate nucleus. The positivity of dentate nucleus neurons for ubiquitin may support the concept of synaptic dysfunction between Purkinje cells and dentate nucleus neurons.