Carbon dioxide recruitment threshold as a predictor of successful weaning in chronic obstructive pulmonary disease patients: A pilot study

Abstract Several methods have been used to predict successful weaning and extubation among chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to determine whether carbon dioxide recruitment threshold (PCO₂RT) can be used as adjunct to conventional weaning parameters to predict early weaning and successful extubation. Twelve COPD patients who were ready to be extubated based on conventional weaning parameters were divided into group A ( n = 7) and group B ( n = 5). Group A were those patients with better weaning parameters and hence a higher probability of successful extubation as compared to group B. Carbon dioxide apnoeic threshold (PCO₂AT) was obtained by hyperventilating the patient using an increment of two breaths per min until apnoea occurs. At this point, the PCO₂AT or the PaCO₂ during said apnoeic period was recorded. A dead space of 150 cc is then added to the circuit until the patient starts to breathe as evidenced by the sensitivity trigger indicator. The PCO₂ obtained at this period is termed PCO₂RT. After weaning for 30 min on a T-tube, another arterial blood gas is determined and this is called the PCO₂SB or the CO₂ level after 30 min on spontaneous breathing. If the PCO₂SB-PCO₂RT difference is high with a sensitivity of 85.71% and specificity of 100% vs sensitivity of 57.14% and specificity of 60% using the conventional weaning parameters. Thus an increase in PCO₂SB at 30 min T-tube is indicative of impending respiratory pump failure and that other causes of failure to wean must be investigated.     

The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.     

Detection of infectious human immunodeficiency virus type 1 in female genital secretions by a short-term culture method

Infectious human immunodeficiency virus type 1 (HIV-1) is difficult to detect in female genital secretions by standard virus culture techniques. To improve detection of cell-free HIV-1 in female genital secretions, we adapted a short-term assay that uses the multinuclear-activation galactosidase indicator (MAGI) assay. When vaginal lavages from HIV-1-infected women were tested with the adapted MAGI assay, 25 (64%) of 39 lavages with detectable, cell-free HIV-1 RNA were shown to have infectious virus. No infectious virus was found in 10 vaginal lavages from HIV-1-infected women with undetectable vaginal viral loads. Significantly (P < 0.01) more lavages from HIV-1-infected women tested positive for infectious virus by the MAGI assay than by standard peripheral blood mononuclear cell (PBMC) coculture, which detected infectious virus in only 6 (17%) of 35 vaginal lavages. Lavages with viral loads of >10,000 copies per lavage yielded significantly (P < 0.01) more positive cultures than those with <10,000 copies by using the MAGI assay. Detection of infectious HIV-1 in vaginal lavages was not associated with the presence of genital tract infections or CD4(+)-T-cell counts. However, although the results were not significant (P = 0.08), the MAGI assay detected infectious virus from more vaginal lavages at a vaginal pH of >/=4.5 than at a pH of <4.5. These results indicate that the MAGI assay is more sensitive than PBMC culture methods for detecting infectious virus in female genital secretions. Accurate measurements of infectious virus in genital secretions will improve studies that evaluate sexual transmission of HIV-1.     

Reliability of body size measurements obtained at autopsy: impact on the pathologic assessment of the heart

Purpose Assessment of body size at autopsy is important for interpreting organ weight measurements and in some cases body identification. The reliability of post-mortem body size measurements, the causes for perturbations in these measurements from their corresponding pre-mortem values, and the impact of such perturbations on heart weight interpretation have not been fully explored. Methods Autopsy body length and weight measurements and pre-mortem height and body weight measurements were compared in 132 autopsies. Clinical records were evaluated for peripheral edema and serum albumin levels. Causes of death, body cavity fluid collections, and heart weights were obtained from the autopsy reports. A subset of patients underwent quantitative post-mortem computed tomography assessment of anasarca. Results At autopsy, body weight differed from the pre-mortem value by 11 ± 1 %, compared with ?0.2 ± 0.3 % for body length (P < 0.0001). The percent change in body weight at autopsy correlated with the presence of peripheral edema (14 ± 2 % vs. 7 ± 2 %, P = 0.01), serum albumin < 3.0 g/dL (16 ± 2 % vs. 7 ± 2 %, P = 0.001), and the degree of anasarca (P = 0.01). In 4 % of autopsies, heart weights were abnormal based on the pre-mortem body weight, but would be classified as normal based on the elevated post-mortem body weight. Conclusions At autopsy, body weight is a less reliable parameter than body length in correlating with the corresponding pre-mortem measurement. Autopsy body weights are elevated in part due to peripheral edema/anasarca. Alterations in body weight at autopsy can confound the interpretation of organ weight measurements.     

Cardiac pathology after valve replacement by disc prosthesis: A study of 61 necropsy patients

Clinical and necropsy observations are described in 61 patients who had one or more cardiac valves replaced with a discoid prosthesis of the Hufnagel type. The most common (31 percent) cause of death among the 45 patients who died early (less than 65 days after operation) appeared to be prosthetic disproportion; that is, the prosthesis was too big for the aorta or ventricular cavity into which it was inserted so that inadequate space was present between the margins of the disc and the endocardium of ventricle or intima of aorta. Prosthetic thrombosis occurred in only 3 of the 45 patients who died early, but poppet movement appeared considerably altered in each. In contrast, thrombi were observed on a prosthesis in 14 of the 16 patients who died late (4 to 47 months [average 21] postoperatively), but in none did the thrombi appear of sufficient size to alter poppet function. Excessive bleeding occurred in 11 (24 percent) of the 45 early deaths and was primarily related to the insertion of a patch in the root of the aorta. Uncorrected valvular disease either by itself or by its ability to alter function of the prosthesis appeared responsible for death in 6 (13 percent) of the 45 patients who died early and in 2 (6 percent) of the 16 who died late. Insertion of a mitral poppet disc in a patient with uncorrected aortic regurgitation, even of mild degree, may be hazardous because the aortic regurgitant jet stream may interfere with proper function of the mitral disc. Likewise, insertion of a poppet disc only in the aortic valve position in a patient with combined aortic and mitral regurgitation may considerably increase the degree of mitral incompetence because the aortic prosthesis is intrinsically obstructive.Disc wear or variance was observed in all but one prosthesis in place for more than 1 year. Although hemolytic anemia of significant degree was not observed in any of the 16 patients who died late, the occurrence of renal hemosiderosis in 13 of the 16 patients indicates that the poppet disc prosthesis is considerably traumatic to erythrocytes. Thus, this type of prosthesis is not an ideal substitute cardiac valve. It clots, despite anticoagulant therapy, it is intrinsically stenotic, portions of it, that is, the disc, degenerate, and it causes hemolysis to erythrocytes.     

Polyreactive antigen-binding B cells in the peripheral circulation are IgD+ and B7−

Polyreactive antibodies are naturally occurring antibodies, primarily of the IgM isotype, that are capable of reacting with a wide variety of different self and non-self antigens. Previously, we reported that a B cell capable of making polyreactive antibody has Ig receptors on its surface that can bind different antigens. The present investigation was initiated to characterize these polyreactive antigen-binding B cells further. A panel of fluorescein isothiocyanate-labeled antigens (insulin, IgG Fc fragment or β-galactosidase) served as probes to select polyreactive antigen-binding B cells by cell sorting. Our experiment revealed that these polyreactive antigen-binding B cells were mainly of the IgD isotype. They expressed high levels of CD40 and major histocompatibility complex class II molecules, but little or no B7-1, B7-2, or Fas. In contrast to the binding of antigens to monoreactive receptors (usually high affinity), the binding of antigens to polyreactive receptors (usually moderate or low affinity) did not up-regulate the expression of B7-1 or B7-2. Antigens that bound to polyreactive receptors, however, were internalized and degraded, although not as efficiently as antigens that bound to monoreactive receptors. Despite the ability of these B7⁻ cells to process antigens, they were not able to activate T cells in a mixed leukocyte reaction. It is concluded that polyreactive antigen-binding B cells have properties that are consistent with the ability to induce immunological tolerance.     

Targeted disruption of the protein tyrosine phosphatase-like molecule IA-2 results in alterations in glucose tolerance tests and insulin secretion

IA-2 is a major autoantigen in type 1 diabetes. Autoantibodies to IA-2 appear years before the development of clinical disease and are being widely used as predictive markers to identify individuals at risk for developing type 1 diabetes. IA-2 is an enzymatically inactive member of the transmembrane protein tyrosine phosphatase family and is an integral component of secretory granules in neuroendocrine cells. To study its function, we generated IA-2-deficient mice. Northern and Western blot analysis showed that neither IA-2 mRNA nor protein was expressed. Physical examination of the IA-2(- /-) animals and histological examination of tissues failed to reveal any abnormalities. Nonfasting blood glucose levels, measured over 6 months, were slightly elevated in male IA-2(-/-) as compared to IA-2(+ /+) littermates, but remained within the nondiabetic range. Glucose tolerance tests, however, revealed statistically significant elevation of glucose in both male and female IA-2(-/-) mice and depressed insulin release. In vitro glucose stimulation of isolated islets showed that male and female mice carrying the disrupted gene released 48% (P < 0.001) and 42% (P < 0.01) less insulin, respectively, than mice carrying the wild-type gene. We concluded that IA-2 is involved in glucose-stimulated insulin secretion.