Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.      

Complex and simple coronary artery stenoses: a new way to interpret coronary angiograms based on morphologic features of lesions

For many years, atherosclerotic coronary artery lesions have been described by angiographers only in terms of location and degree of narrowing. However, it has become apparent that coronary stenoses generally have distinct morphologic features that can be recognized at angiography and that allow them to be classified as either "simple" or "complex" plaques. Complex plaques are those characterized by ulcerated or ruptured surfaces, subintimal hemorrhage, superimposed partially occluding thrombi, recanalized thrombi, or some combination. Pathologic studies have shown a very high frequency of these lesions at sites of total thrombotic occlusion of coronary arteries. Clinical and angiographic studies have demonstrated a high frequency of such lesions in living patients with both unstable angina and acute myocardial infarction. The presence of complex stenoses has also been found to increase the risk of future myocardial infarction. Plaque morphology thus appears to significantly affect the prognosis of patients with coronary disease and should be carefully evaluated in interpretation of all coronary angiograms.     

The effect of pharmacoeconomics on company research and development decisions

There is a strong rationale for integrating pharmacoeconomics into research and development (R&D) project selection and termination decisions. The average cost for the typical new drug introduction now exceeds $US300 million. Furthermore, a growing proportion of phase III projects are terminated because of economic factors relative to efficacy and safety concerns. While the use of pharmacoeconomic studies by payers is still evolving, the pressures on firms to show that new products are cost effective will only intensify in future periods. Accordingly, it is important for firms to begin analysing the cost effectiveness of new drug candidates early in the R&D process. The cost effectiveness of a new therapy can be simulated prior to clinical testing using different assumptions about the efficacy, tolerability, pricing and formulation of the new therapy. These models can be refined and updated as data become available from clinical testing and other sources. A key objective is to make uncompetitive projects fail sooner while channelling development resources to projects with high expected returns. Cost-effectiveness analysis should be an integral component of the firms's strategic action plan and its return on investment analyses.     

Expression of an inducible nitric oxide synthase gene in rainbow trout Oncorhynchus mykiss

Using oligonucleotide primers based on mammalian nitric oxide synthases (NOS), expression of an inducible NOS (iNOS) gene was detected in head kidney and gill tissue of bacterially-challenged rainbow trout. Three overlapping fragments were amplified by RT-PCR and used to construct a contiguous sequence of 1410bp, with high nucleotide homology to iNOS in birds (61%) and mammals (57-59%). The nucleotide sequence translated in one reading frame to produce a partial peptide containing 470 amino acids, with 69-71% amino acid homology with mammalian iNOS, 81% homology with chicken iNOS and 85% homology with a partial (492bp) goldfish iNOS sequence. In vitro stimulation of head kidney macrophages with LPS also induced expression of the trout iNOS RNA, with optimal expression seen using 20-50 microg/ml LPS at 2h to 6h post-stimulation. The evolutionary and functional significance of the trout iNOS sequence are discussed.     

Mediating phosphorylation events in the vanadium-induced respiratory burst of alveolar macrophages

Occupational exposure by inhalation to vanadium-containing particles such as residual oil fly ash results in respiratory tract inflammation. This inflammation, characterized by abundant neutrophilia, appears to be initiated by alveolar macrophages (AMs) encountering particles and the subsequent release of proinflammatory cytokines. Intracellular signaling events in these cells in response to particles or their components are largely unknown. We investigated two immediate responses of AMs to vanadium exposure in vitro, the production of reactive oxygen intermediates (ROI) or respiratory burst (RB), and the tyrosine phosphorylation of cellular proteins. Macrophages exposed in vitro to 100 microM vanadyl chloride/1 microCi 48V incorporated 8.3% of the metal after 30 min. Exposure of AMs to increasing concentrations of sodium metavanadate resulted in a dose-dependent increase in production of ROI as measured by dichlorofluorescin oxidation. The lowest dose yielding a significant response was 50 microM, whereas 1000 microM increased RB activity by 173%. NADPH oxidase inhibitors deoxy-D-glucose (100 mM) and diphenylene iodonium (25 microM) reduced the metavanadate-induced RB by 62 and 71%, respectively, implicating NADPH oxidase as the primary cellular source of ROI. Enhanced cerium chloride oxidation in response to metavanadate localized to the plasma membrane consistent with increased NADPH oxidase activity. Pretreatment of AMs with the epidermal growth factor receptor inhibitor, tryphostin B50 (10 microM), reduced the metavanadate-induced RB, but did not influence overall tyrosine phosphorylation. Metavanadate and H2O2 exposure greatly increased overall tyrosine phosphorylation, yielding a similar but distinguishable pattern of phosphorylation in these cells. These observations demonstrate that in vitro metavanadate exposure regulates two distinct, yet related intracellular signaling pathways important in initiating inflammatory responses in these cells: (1) activation of the NADPH oxidase complex with subsequent increased ROI synthesis, and (2) enhanced tyrosine phosphorylation of cellular proteins.     

Osteoradionecrosis of the anterior cranium

Osteoradionecrosis occurs in approximately 10% to 15% of patients following radiation therapy for head and neck cancer. In these patients, it is most commonly reported in sites involving the mandible, but it has also been reported in the maxilla, sphenoid, and temporal bones. The majority of these cases are related to some type of trauma such as dental extraction or intraoral biopsies. However, approximately 40% of these entities occur spontaneously and are felt to be secondary to cell kill in intermediate tissues such as bone and periosteum. Our literature review yielded no previously reported cases of osteoradionecrosis involving the anterior cranium. The following two cases present patients who experienced osteoradionecrosis of their frontal bone flaps following subcranial approaches for tumor resection. Both patients suffered from carcinomas involving the ethmoid sinuses; one tumor was a moderately well-differentiated squamous cell carcinoma, the other a mucinous adenocarcinoma. One patient's radiation therapy consisted of external beam photons; the other patient received external beam neutrons. Treatment for these patients, as well as possible causative factors regarding their osteoradionecrosis, are discussed.     

Congenital pulmonary atresia with ventricular septal defect: angiographic and surgical correlates

Of 181 patients with severe congenital pulmonary atresia and ventricular septal defect or "type IV truncus" (an obsolete term), all but 11% had true central pulmonary arteries. These arteries were demonstrable by large serial biplane angiograms using multiple selective injections into collateral vessels, frequent photographic subtraction, and occasional pulmonary vein-wedge angiograms. These techniques are extremely important for accurate diagnosis and in planning corrective or palliative surgery, which was done in 77% of patients with pulmonary arteries.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Rising incidence of type 1 diabetes in Scottish children, 1984-93. The Scottish Study Group for the Care of Young Diabetics

OBJECTIVES: To calculate the incidence of type 1 diabetes in Scottish children aged less than 15 years between 1984 and 1993; to examine changes in incidence; and to calculate the prevalence of diabetes at the end of this period. DESIGN: Three data sources were used to construct the Scottish Study Group for the Care of Young Diabetics register: active reporting of all new cases; reports from the Scottish Morbidity Register 1; and local registers. SUBJECTS: All children resident in Scotland diagnosed with primary insulin dependent diabetes mellitus when less than 15 years of age between 1984 and 1993. MAIN OUTCOME MEASURES: Annual incidence and prevalence rate for Scotland; time trend in incidence over the 10 years; differences in incidence between the three different age groups; and completeness of the register. RESULTS: The average annual incidence for Scotland was 23.9/100,000 children. The prevalence rate was 1.5/1000 in 1993. A total of 2326 cases was identified from the three sources. Capture-recapture analysis suggests a case ascertainment of 98.6%. The annual incidence rates increased at a rate of 2% each year (rate ratio = 1.02, 95% confidence interval (CI) 1.01 to 1.03). The incidence was higher in boys than girls (rate ratio = 1.08, 95% CI 1.00 to 1.18), and the incidence rates increased with age: 15.3/100,000/year for age 0-4 years, 24.4/ 100,000/year for age 5-9 years, and 31.9/ 100,000/year for age 10-14 years. CONCLUSIONS: The incidence of type 1 diabetes in Scotland is increasing and the prevalence is relatively high. These findings have important implications for health service resource allocation. The Scottish Study Group for the Care of Young Diabetics' register provides a base for monitoring and research.