Human joining peptide: a proopiomelanocortin product secreted as a homodimer.

The human (h) POMC gene sequence predicts a 30 amino acid joining peptide (JP) separating the N-terminal fragment [POMC(1-76) or hNT] and ACTH within their common precursor. We used an anti-serum directed against the amidated COOH-terminal end of mouse JP to develop a RIA for the predicted hJP molecule. Immunoreactive JP was detected in tissue extracts from human normal pituitary, ACTH-secreting pituitary- and nonpituitary tumors, and in plasma from patients with ACTH hypersecretory syndromes. Its molar concentration was of the same order of magnitude as, and correlated with, that of the other POMC peptides. Gel exclusion chromatography in 1% formic acid and 6 M guanidine-HCl revealed a predominant immunoreactive material with an apparent mol wt of ca. 6000. After reduction with dithiothreitol this material was recovered in an elution volume identical to that of purified hJP and corresponding to a mol wt of ca. 3000. These data show that POMC processing generates a COOH terminally amidated hJP predominantly secreted as a homodimer, probably through disulfide bonding between the single Cys9 residue of two molecules.

Pulmonary function tests in HIV-infected patients.

OBJECTIVE: To evaluate alterations in lung function during the course of HIV infection. DESIGN: Total lung capacity (TLC), the ratio of forced expiratory volume in one second to vital capacity (FEV1/VC), the carbon monoxide transfer factor (TLCO) and the alveolar-arterial oxygen gradient [delta (A-a)O2] were determined in this retrospective study. PATIENTS: Pulmonary function tests (PFT) were performed on 331 patients at various stages of HIV infection. Patients with a history of intravenous drug use or Kaposi's sarcoma were excluded. RESULTS: No significant differences were observed between the results for asymptomatic patients and those with AIDS-related complex (ARC). TLC, delta (A-a)O2 and TLCO were greatly altered in patients with acute Pneumocystis carinii pneumonia (PCP). No significant differences were observed in the TLC, delta(A-a)O2 or TLCO results between AIDS patients with no history of PCP and those with a history of a single episode of PCP. TLCO was significantly lower (P < 0.001) in AIDS patients with one previous episode of PCP than in the patients with ARC. Interestingly, both TLC and TLCO were significantly lower in the AIDS patients with no history of PCP than in the patients with ARC. Follow-up of 28 patients at different stages of HIV infection confirmed the alteration of PFT results in the late stages. CONCLUSIONS: The reasons for alterations in PFT results in PCP-free AIDS patients remain to be determined. Our findings suggest that PFT can provide valuable information throughout the course of HIV infection, particularly with regard to the indication for bronchoalveolar lavage.

Alteration of the alveolar-capillary membrane diffusing capacity in chronic left heart disease.

During left heart disease, the chronic increase in pulmonary capillary wedge pressure (PCWP) results both in vascular alterations with increased pulmonary vascular resistance (PVR), and in progressive thickening of the alveolar-capillary membrane, which diffusing capacity (Dm) is reduced. However, the total lung diffusing capacity for carbon monoxide (TLco) is inconstantly impaired, depending on the degree of pulmonary congestion. We evaluated the relation between the pulmonary hemodynamic repercussions of chronic heart disease and the 2 components of TLco, i.e., Dm and capillary blood volume. Forty-seven patients with chronic left heart disease (28 with valve disease, 19 with cardiomyopathy) underwent right heart catheterization with determination of PCWP and PVR. Pulmonary function tests, including spirometry, determination of TLco, and of its 2 components (percentage of predicted values) were performed in patients and in 15 healthy subjects. TLco and Dm, but not capillary blood volume, were significantly decreased in patients. Dm was related to PVR (p = 0.0006), and was markedly reduced in patients with high PVR (> or = 3 Wood U): 54 +/- 8% vs 80 +/- 19% in patients with normal PVR (p <0.0001). Dm < or = 66% identified all high PVR patients (sensitivity = 100%, specificity = 77%). Capillary blood volume was related to PCWP (p = 0.02), and was increased in patients with high PCWP (> 15 mm Hg): 126 +/- 30% vs 99 +/- 23% (p <0.01), but with a marked overlap. TLco values, although reduced in patients with high PVR (p <0.001), were not predictive of high PVR or high PCWP. Determination of Dm allows a more accurate detection of pulmonary hypertension complicating chronic left heart disease than the other pulmonary parameters.

Pulmonary tolerance of prophylactic aerosolized pentamidine in human immunodeficiency virus-infected patients.

The effects of primary and secondary long-term prophylaxis of Pneumocystis carinii pneumonia with aerosolized pentamidine on pulmonary function in HIV+ patients were evaluated. Eighty-one patients, none of whom were drug addicts or had pulmonary Kaposi's sarcoma, were studied. Fifty patients were receiving AP as secondary prophylaxis, 36 monthly and 14 twice-monthly; eight patients with a history of PCP served as control subjects. Twenty-three patients were receiving AP as primary prophylaxis, 12 monthly and 11 twice-monthly. Pulmonary function tests, including spirometry, lung transfer capacity for carbon monoxide (Tlco) and alveolar-arterial oxygen gradient (P[A-a]O2) were evaluated at M1, ie, one month after the diagnosis of PCP, or at the beginning of the AP prophylaxis, and then at three-month intervals (M4 to M13). No differences were observed in the results of spirometry or P(A-a)O2. Among the patients receiving secondary prophylaxis, a significant increase (paired Student's t-test) in Tlco occurred at M7 compared to M1 in the group receiving monthly administrations (p less than 0.01) and in the untreated control group (p less than 0.05); there was no significant difference in Tlco at M13 compared to M1 in the 12 patients who received monthly administrations for this period or at M7 in the 14 patients receiving AP twice-monthly. No significant difference in Tlco was observed at M7 in the primary prophylaxis groups. These results indicate that pulmonary tolerance of AP, as reflected by pulmonary function tests, is good.

Positron Emission Tomography and Computer Tomography (PET/CT) in Prostate, Bladder, and Testicular Cancers

Positron emission computed tomography (PET) is a functional, noninvasive method for imaging regional metabolic processes that is nowadays most often combined to morphological imaging with computed tomography (CT). Its use is based on the well-founded assumption that metabolic changes occur earlier in tumors than morphologic changes, adding another dimension to imaging. This article will review the established and investigational indications and radiopharmaceuticals for PET/CT imaging for prostate cancer, bladder cancer and testicular cancer, before presenting upcoming applications in radiation therapy.

[Mass spectrum analysis of expired and alveolar gas during separate bronchospirometry]. / Analyse au spectromètre de masse du gaz expiré et du gaz alvéolaire au cours de la bronchospirométrie séparée.

It is possible to measure with a mass spectrometer the oxygen and carbon dioxide pressure in expired gas and alveolar gas in each lungs during a separate bronchospirometry. In 15 cases out of 26 (of which 21 had broncho-pulmonary cancers) it was possible to trace serious disorders of the alveolar-capillary exchanges in the diseased lung, probably related to an altered ventilation-perfusion relationship. This technique brings more data to the physio-pathologist than the plain measurement of the oxygen consumption of the diseased lung.

High-performance liquid chromatographic method for the determination of cefpodoxime levels in plasma and sinus mucosa.

A selective HPLC method is described for the determination of cefpodoxime levels in plasma and sinus mucosa. Sample preparation included solid-phase extraction with a C8 cartridge. Cefpodoxime and cefaclor (internal standard) were eluted with methanol and analyzed on an optimised system consisting of a C18 stationary phase and a ternary mobile phase (0.05 M acetate buffer pH 3.8-methanol-acetonitrile, 87:103, v/v) monitored at 235 nm. Linearity and both between- and within-day reproducibility were assessed for plasma and sinus mucosa samples. Inter-assay coefficients of variation were lower than 13.6% (n = 10) for plasma (0.2 micrograms/ml) and lower than 12.4% (n = 5) for sinus mucosa (0.25 micrograms/g). The quantification limit was 0.05 micrograms/ml for plasma and 0.13 micrograms/g for tissue. The method was used to study the diffusion of cefpodoxime in sinus mucosa.

[Study upon oxygen conveyance in severe anaemia. About a very serious case of hemolytic anaemia which led to a myocardial infarct (author's transl]. / Transport de l'oxygène lors des anémies sévères. Une observation d'anémie hémolytique grave compliquée d'infarctus du myocarde.

To understand the orientation the metabolism of a sick person whose arterial content in oxygen had collapsed (CaO2 reaching 1,9 vol/100 ml) the cardiac output and the rate myocardic extraction of the lactates have been measured. The cardiac index was very high 7,4 l/m/m2 and in spite of a low D (a-v) (2,5 vol/ml) the consumption of oxygen was normal. Three days after a first measure the steep (or brutal) fall of the cardiac and the reversal of the rate of myocardic extraction of lactate led up to diagnose an acute coronary insufficiency. The electrocardiogramm only cortoborated the myocardic necrosis in a second time. This result invites (or calls for) a constant electrographic watching of sick persons who suffer from severe anaemia, even with sane coronary vessels, to avoid diagnosing coronary insufficiency through so circuitous means.

[Study of pulmonary leucostasis by measurement of the alveolo-arterial CO2 difference (author's transl)]. / Etude de la leucostase pulmonaire par mesure de la différence artério-alvéolaire en CO2.

In order to study pulmonary leucostasis in 18 leukemic subjects, the ventilatory flow from ventilated nonperfused zones (VFVNZ) was measured using alveolo-arterial CO2 difference (28 times). This method proved to be simple and accurate in the follow-up of the patients. The number of white cells necessary to increase the VFVNZ by 1% is very different from one histologic type to another. These results are in agreement with in vitro observations.

Exercise intolerance in patients with McArdle's disease or mitochondrial myopathies.

OBJECTIVES: To assess respiratory and metabolic adaptations in patients with phosphorylase deficiency and mitochondrial myopathies using maximal exercise tests. PATIENTS AND METHODS: Five patients with McArdle's disease and five patients with mitochondrial myopathies performed the same incremental maximal exercise test. Their respiratory gas exchanges and the variation of the venous blood metabolites--lactate (LACT), pyruvate (PYR), alanine (ALA), ammonia (NH3)--were studied in comparison with the results of fourteen control subjects who performed the same test. RESULTS: Compared with controls, the two groups of patients displayed a similar significant decrease of their maximal VO2. In McArdle's patients the limitation of the maximal oxygen consumption was associated with a low respiratory exchange ratio (RER), a high VE/VO2, and characteristic metabolic data: no rise of LACT and PYR, a decrease of ALA and an important rise of NH3. In mitochondrial myopathies low VO2 max were due to a leftwards shift, i.e. towards low powers of exercise, of LACT, PYR, NH3 and ALA values. However the pattern of increase of LACT, PYR and NH3, exponential, and of ALA, linear, as well as respiratory exchange ratios were similar to control values. In this case, the limitation of oxygen consumption was due to a lack of the usual substrate, pyruvate. Low respiratory exchange ratio demonstrated that the muscle metabolism had a tendency to shift to lipid oxidation. CONCLUSION: These results suggest that patients with McArdle's disease may improve their muscle energy production by endurance training which enhances lipid metabolism, whereas in mitochondrial myopathies, the energy production by oxidation of pyruvate or lipids may be improved only by enzymatic substitution.

Unexplained fever and chronic fatigue: abnormal circadian temperature pattern.

OBJECTIVES: Standard clinical and biological investigations can be used to determine the origin of persistent and moderate fever in a large number of otherwise asymptomatic patients. However, in a small proportion of cases, isolated fever and fatigue persist despite the absence of detectable organic malfunction. This study was conducted to investigate the circadian thermic pattern in patients with apparently unexplainable fever and chronic fatigue and in those with fever of recognized origin. METHODS: We recorded central temperature continuously for 24 hours in patients with moderate fever of both unexplained and recognized origin, and in a control group of healthy volunteers. A Fourier series was used for harmonic analysis. RESULTS: Thermic patterns specific to the three groups were identified by statistical and factorial analysis. The patients with fever of unknown origin and chronic fatigue were clearly characterized in terms of the phase, amplitude of the first (fundamental) harmonic and minimum circadian temperature. CONCLUSION: The abnormal central temperature pattern in these patients may prove to be an important step in the management of febrile patients.

Effects of nifedipine and diltiazem on pharmacokinetics of cefpodoxime following its oral administration.

We compared the effects of nifedipine and diltiazem on the uptake of cefpodoxime proxetil (CP). The study was aimed at establishing the impact of increased mesenteric blood flow due to calcium channel blockers on passive transport. Twelve volunteers were given CP (200 mg) orally in a crossover design. The absorption, disposition, and elimination parameters of cefpodoxime were compared among the following three treatment groups: CP alone, CP following oral administration of diltiazem (60 mg), or CP following oral administration of nifedipine (20 mg). No statistically significant difference in pharmacokinetic parameters was observed between the three treatment groups.