In vitro studies of intragastric digestion

Following consumption of a meal, 99% of the large food particles are emptied only after intragastric fragmentation has reduced their diameter to less than 2 mm. Anin vitro model was constructed to evaluate some of the factors which may play a role in the process of intragastric digestion. Gastric mixing of food was simulated in a silicone rubber tube (ID 19 mm) placed in a peristaltic pump. Peristaltic waves progressed upwards along the tube at a frequency of 0, 1, or 3/min, reducing the internal diameter of the tube to 5 mm. Cooked chicken liver particles (2–2.8 mm in diameter) were placed in the tube with one of the following: (1) 150 mM NaCl, (2) 150 mM HCl with or without pepsin, or (3) phosphate buffer at pH 7, 5.4, or 2.6 + pepsin. After 30 min, the extent of particle reduction and of solubilization of proteins were determined and expressed as percent of the initial liver weight. The diameter of liver particles was reduced to a greater extent in NaCl than in pH 7 buffer or acid solutions with or without pepsin. In contrast, the amount of proteins solubilized was enhanced two- to threefold by acid pepsin solutions compared to NaCl or pH 7 phosphate. The presentin vitro studies suggest that changes in motor and/or secretory activity of the stomach significantly modify intragastric digestion.     

Pennsylvania's medically uninsured population: findings from a statewide survey

Pennsylvania is currently considering legislative options to expand coverage and improve access to medical care for state residents who lack health insurance. Relevant data are presented from a telephone survey of 10,809 Pennsylvania households. Almost nine percent (8.5%) of the state's population lacks health insurance, representing over one million people. Those most likely to be uninsured are children and young adults, non-whites and the poor. A substantial number of poor people are not covered by the state's Medicaid program. The uninsured report poorer health status, more obstacled to receiving care and greater use of hospital services for primary care.     

The topographical and neuroanatomical distribution of neurofibrillary tangles and neuritic plaques in the cerebral cortex of patients with Alzheimer's disease.

The distribution of neurofibrillary tangles (NFTs) and neuritic plaques (NPs) was mapped in 39 cortical areas of 11 brains of patients with Alzheimer's disease (AD). Whole hemisphere blocks were embedded in polyethylene glycol (Carbowax), sectioned coronally, and stained with thioflavin S and thionin. The densities of NFTs and NPs were assessed using a numerical rating scale for each area. Scores were grouped by type of cortex and by lobe for statistical analysis. Highly significant differences were obtained. For example, limbic periallocortex and allocortex had more NFTs than any other type of cortex. In descending order, the density of NFTs was as follows: periallocortex (area 28) greater than allocortex (subiculum/CA1 zones of hippocampal formation, area 51) greater than corticoid areas (accessory basal nucleus of amygdala, nucleus basalis of Meynert) greater than proisocortex (areas 11, 12, 24, 23, anterior insula, 38, 35) greater than nonprimary association cortex (32, 46, superior temporal sulcus, 40, 39, posterior parahippocampal cortex, 37, 36) greater than primary sensory association cortex (7, 18, 19, 22, 21, 20) greater than agranular cortex (44-5, 8, 6, 4) greater than primary sensory cortex (41-2, 3-1-2, 17). The laminar distribution of NFTs tended to be selective, involving primarily layers III and V of association areas and layers II and IV of limbic periallocortex. There were far more NFTs in both limbic and temporal lobes than in frontal, parietal, and occipital lobes. In general, NPs were more evenly distributed throughout the cortex, with the exceptions of limbic periallocortex and allocortex, which had notably fewer NPs than other cortical areas. Temporal and occipital lobes had the highest NP densities, limbic and frontal lobes had the lowest, and parietal lobe was intermediate. No significant left-right hemispheric differences for NFT or NP densities were found across the population, and there was no relationship between duration of illness and densities of NFTs or NPs. The regional and laminar distribution of NFTs (and, to a lesser degree, that of NPs) suggests a consistent pattern of vulnerability within the cerebral cortices that seems correlated to the hierarchies of cortico-cortical connections. The higher-order association cortices, especially those in the anterior and ventromedial sectors of temporal lobe, are the most vulnerable, while other cortices appear less vulnerable to a degree commensurate with their connectional "distance" (i.e., synapses removed) from the limbic areas.     

Pharmacokinetics of methyldopa in healthy man

Summary The pharmacokinetics of 2-¹⁴C-L--methyldopa have been investigated in five healthy volunteers following intravenous and oral administration. In the intravenous study a bi-phasic plasma concentration curve was found both for chemically determined -methyldopa and for radioactivity. The plasma level of radioactivity differed significantly from chemically determined drug, a pattern which was also found in urine. This suggests the presence of unidentified metabolite(s). The difference between plasma disappearance and urine recovery of -methyldopa and radioactivity during the first 4 h after injection suggests distribution to an extravascular compartment. Plasma half-lives of total radioactivity and of unchanged drug were calculated. In three subjects, pharmacokinetic parameters for a two-compartment open body model were calculated from urine and plasma data. Urinary recovery of radioactivity was almost complete within 48 h after intravenous administration. After oral administration, however, only about 40 per cent of the radioactive dose was recovered in the urine, and it contained approximately equal amounts of unconjugated methyldopa, acid-labile conjugated methyldopa and unidentified metabolite(s). The acid-labile conjugate was found only after oral administration, which supports the theory of a mucosal conjugation process. The lack of acid-labile conjugated drug either in the plasma or urine after intravenous injection indicates that there is no enterohepatic circulation of this drug.     

Outcome of allogeneic hematopoietic stem-cell transplantation in adult patients with acute lymphoblastic leukemia: no difference in related compared with unrelated transplant in first complete remission.

PURPOSE: The role of unrelated allogeneic stem-cell transplantation in acute lymphoblastic leukemia (ALL) patients is still not clear, and only limited data are available from the literature. We analyzed factors affecting clinical outcome of ALL patients receiving a related or unrelated stem-cell graft from matched donors. PATIENTS AND METHODS: The total study population was 264 adult patients receiving a myeloablative allogeneic stem-cell transplant for ALL at nine bone marrow transplantation centers between 1990 and 2002. Of these, 221 patients receiving a matched related or unrelated graft were analyzed. One hundred forty-eight patients received transplantation in complete remission; 62 patients were in relapse; and 11 patients were refractory to chemotherapy before transplant. Fifty percent of patients received bone marrow, and 50% received peripheral blood stem cell from a human leukocyte antigen-identical related (n = 103), or matched unrelated (n = 118) donor. RESULTS: Disease-free survival (DFS) at 5 years was 28%, with 76 patients (34%) still alive (2.2 to 103 months post-transplantation), and 145 deceased (65 relapses, transplant-related mortality, 45%). We observed an advantage regarding DFS in favor of patients receiving transplantation during their first complete remission (CR) in comparison with patients receiving transplantation in or after second CR (P =.014) or who relapsed (P <.001). We observed a clear trend toward improved survival in favor of B-lineage ALL patients compared with T-lineage ALL patients (P =.052), and Philadelphia chromosome-positive patients had no poorer outcome than Philadelphia chromosome-negative patients. Total-body irradiation-based conditioning improved DFS in comparison with busulfan (P =.041). CONCLUSION: Myeloablative matched related or matched unrelated allogeneic hematopoietic stem-cell transplantation in ALL patients should be performed in first CR.     

Population variations in the initial treatment of non-small-cell lung cancer.

PURPOSE: Dissemination of recommended therapies for non-small-cell lung cancer (NSCLC) have not been described comprehensively. We report the patterns of initial therapy focusing on the investigation of differences in receipt of recommended therapies according to multiple clinical and nonclinical patient characteristics. METHODS: A population-based random sample of newly diagnosed NSCLC patients diagnosed in 10 separate geographic areas was collected in 1996 (n = 898). Data were obtained from medical records. Multiple logistic regression was used to assess the use of recommended therapies. RESULTS: Overall, 52% of NSCLC patients received recommended therapy. Approximately 69%, 48%, and 41% of patients with stages I and II, III, or IV NSCLC received recommended therapy, respectively. For all stages combined, the use of recommended therapy was significantly inversely associated with age and stage at diagnosis. Recommended therapy also was more common in white versus black patients, and in married versus single patients. Stage-specific analyses revealed a significant decline in the use of recommended surgery with increasing age at diagnosis for early-stage NSCLC only, and a significantly lower use of recommended therapy (primarily chemoradiotherapy) for stage III black and Hispanic patients compared with white patients. CONCLUSION: The overall use of recommended therapies for NSCLC is low. Large variations exist in the use of such therapies according to age, race or ethnicity, and marital status. Research combining medical record reviews with other sources of data is needed to better understand the contributions of both patient preferences and physician judgment to these treatment variations.     

Metastatic testicular cancer presenting as spinal cord compression: report of two cases

BACKGROUND: Testicular cancers are heterogenous neoplasms often found in young adults. They tend to metastasize to the chest, retroperitoneum, or neck, but rarely to the long bones or skeleton. However, they can cause neurologic compromise and should be considered in young male patients who present with symptoms of a spine lesion and no known primary cancer. METHODS: Two patients presented with back pain and a rapid progression of lower extremity weakness. Both underwent radiographic workup and emergency surgery. Metastatic workup revealed testicular cancer and widespread metastases. RESULTS: Both patients improved neurologically after surgery, but neither regained the ability to ambulate independently. They both underwent chemotherapy. One patient is alive at 1 year follow-up; the other died 9 months after surgery of widespread metastases. CONCLUSIONS: Vertebral metastases from testicular tumors, although rare, should be considered in young men presenting with spinal cord compression. Work-up should include magnetic resonance imaging (MRI) of the spine and computed tomography (CT) of the chest, abdomen, and pelvis. Urgent intervention may be required, as these two cases show that loss of neurologic function can be rapid and permanent.