Immediate and short-term cellular and biochemical responses to pulmonary single-dose studies of insulin and H-MAP.

PURPOSE: It was previously reported that co-administration of H-MAP to the airways of the lungs significantly influenced the absorption, disposition. and effect of insulin in a dose-dependent fashion. Doses of H-MAP (16 mg/kg) and insulin (1.3 U/kg) required to achieve maximum pharmacokinetic and pharmacodynamic responses were determined. The purpose of the present study was to evaluate the effects of insulin and H-MAP spray-instilled (SI) to rats on the physiology of the lung. A short-term, single-dose study of insulin alone and combined with H-MAP was performed. METHODS: Solutions of either insulin (INS), H-MAP, or insulin plus H-MAP (INMA) were SI to the lungs of rats. Lipopolysaccharide solution (LPS) and sodium dodecyl sulfate solution (SDS) were used as positive controls. and normal saline (SAL) was used as negative control. Animals were sacrificed at various time points and bronchoalveolar lavage (BAL) was conducted. BAL fluid was analyzed for local markers of lung injury, such as total cell numbers, differential cell count, total protein content and enzyme activities of lactate dehydrogenase (LDH), alkaline phosphatase (ALP) and N-acetyl glucosaminidase (NAG). RESULTS: SI of any solution, including normal saline, seems to have a minor but detectable effect on the normal physiology of the lung. SI of positive control solutions resulted in most markers of immunity and lung injury being significantly elevated, notably enzyme activity and white cell infiltrate. In contrast, SI of INS produced a response similar to that of SAL. SI of INMA resulted in a small transient response characterized by a slight increase in the proportion of neutrophils at 24 h, which decreased with time and was comparable to that of SAL at 72

Facilitation of pulmonary insulin absorption by H-MAP: pharmacokinetics and pharmacodynamics in rats.

PURPOSE: Several low molecular weight amino acids have previously been reported to enable the oral delivery of proteins. In the present studies, the effect of H-MAP (hydroxy methyl amino propionic acid) on the pharmacokinetics (PK) and pharmacodynamics (PD) of porcine insulin delivered to the lungs of rats by spray-instillation (SI) has been determined. METHODS: Aliquots (100 microl) of increasing doses of porcine insulin alone (0.26, 1.3, 2.6, 13, and 26 U/kg) or combined with increasing doses of H-MAP (5, 10, 16, and 25 mg/kg), at pH 7.2-7.6 were administered intratracheally to fasted anesthetized rats using a micro spray-instillator. Blood samples were collected from the jugular vein at specified intervals and the plasma concentrations of insulin and glucose were determined. The PK and PD of porcine insulin alone following subcutaneous (SC) administration of increasing doses were also determined. RESULTS: The PK of insulin administered either by SI to the lungs or SC injection were absorption rate dependent, resulting in post-peak half-lives 10 to 25-fold greater than the reported intravenous elimination half-life (3 min). The relative bioavailability (F') of insulin administered alone by SI varied from 23.8 to 80% for the lowest and highest insulin dose, respectively. Co-administration of H-MAP and insulin to the lungs significantly changed the PK and PD of insulin in a dose dependent fashion. Maximum PK and PD responses were obtained at an H-MAP dose of 16 mg/kg and an insulin dose of 1.3 U/kg. At this combination, the relative bioavailability of insulin was increased more than 2.5 fold, maximum concentration (Cmax) increased 2-fold and the minimum plasma glucose concentration (%MPGC) was reduced more than 2-fold with respect to same dose of insulin alone. A greater total reduction in plasma glucose (%TRPG0-->t) was achieved for H-MAP/insulin combination (66+/-5%) compared to insulin alone (47+/-10 %). CONCLUSION: H-MAP has potential for increasing the pulmonary bioavailability of insulin administered through the lungs.

Lymphoglandular bodies in fine-needle aspiration cytology smears.

Lymphoglandular bodies (hyaline bodies or lymphoid globules), when found in cytology smears from fine-needle aspirates, have long been accepted as being diagnostic of lymphoid tissue. To investigate the validity of this association as it relates to malignant tumors, we examined cytologic smears from 132 fine-needle aspirates of malignant neoplasms. Three experienced observers independently scored Diff-Quik-stained smears as to cellularity and number and size of lymphoglandular bodies. Discrepancies were resolved by consensus. Results of the fine-needle aspiration biopsies revealed 6 of 104 nonlymphoid malignancies with easily identifiable lymphoglandular bodies (defined as > 2 lymphoglandular bodies per high-power field) and 3 with numerous lymphoglandular bodies (> 10 per high-power field). These tumors consisted of two cases of small-cell carcinoma, four non-small-cell carcinomas, one ganglioneuroblastoma, one melanoma, and one seminoma. The tumors had few, if any, lymphocytes. Of the 28 lymphomas, 5 had easily identifiable lymphoglandular bodies and 19 had numerous lymphoglandular bodies. Although lymphoglandular bodies in the background of cytologic smears taken from malignant tumors are useful in alerting the pathologist to the possibility of lymphoma, there are exceptions.

Mycobacteria can be seen as "negative images" in cytology smears from patients with acquired immunodeficiency syndrome.

The cytologic diagnosis of mycobacterial infections has historically depended on the recognition of the characteristic granulomatous or purulent host response and the identification of acid-fast bacilli with special stains. However, immunocompromised patients with infections may not mount the expected response and the pathologist must have a high index of suspicion for the presence of organisms. We report the cytology findings from three patients with acquired immunodeficiency syndrome in which mycobacteria were seen on the routine modified Wright-stained (Diff-Quik) slides without special stains in the absence of granulomatous inflammation. The organisms appeared as negative images--unstained, rodshaped structures against the deep blue background of the stain. The findings were confirmed with Ziehl-Neelsen stain and culture. Implications for patient management are discussed.

Segmental medullary sponge kidney mimicking a renal mass.

We report an unusual case of a medullary sponge kidney that presented clinically and radiologically as a renal mass. Histopathological study after nephrectomy proved the mass to be consistent with segmental medullary sponge kidney.