Daily variation in circulating cytokines and acute-phase proteins correlates with clinical and laboratory indices in community-acquired pneumonia

Our objective was to investigate the initial levels of circulating proinflammatory cytokines, such as interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha), of certain acute-phase proteins, such as C-reactive protein (CRP), fibrinogen (FBN) and albumin, and of the glycoprotein fibronectin at presentation and their daily variation during the clinical course of community-acquired pneumonia (CAP) in relation to clinical and laboratory indices of infection. Thirty otherwise healthy hospitalized patients aged 48 +/- 3 years (mean +/- SEM) and with bacteriologically confirmed CAP were studied prospectively. IL-1 beta and IL-6 were found to be 15-fold higher on admission (122 +/- 9 pg mL-1 and 60 +/- 4 pg mL-1 respectively), whereas TNF-alpha was three-fold higher (102 +/- 5 pg mL-1) than those of controls, all of them showing a decline towards normal. Initial CRP levels were increased 90-fold (416 +/- 1 mg L-1), whereas fibronectin levels were reduced (242 +/- 9 mg dL-1). The presence of parapneumonic effusion was associated with a higher TNF-alpha serum level (127 +/- 7 vs. 86 +/- 4 pg mL-1, P = 0.0002), a more rapid daily decline in TNF-alpha (-7.2 +/- 0.7 vs. -3.8 +/- 0.5 pg mL-1 day-1, P = 0.0005), a slower rate of decline in CRP (-42.8 +/- 3.0 vs. -54.6 +/- 3.0 mg L-1 day-1, P = 0.02) and a slower rate of increase in FBN (5.9 +/- 1.0 vs. 11.7 +/- 1.0 mg dL-1 day-1), P = 0.001]. Furthermore, daily progression of serum levels of cytokines and acute-phase proteins correlated strongly with pyrexia, erythrocyte sedimentation rate (ESR), neutrophil count, alveolar-arterial oxygen difference and radiographic resolution, clinically manifested by improvement in the patients' condition.     

Postvasectomy residual sperm pregnancy

A pregnancy occuring within a few months after a successful vasectomy is sometimes attributed by a skeptical physician to sexual involvement by the spouse with a nonvasectomized man. This assumption may be unjustified because of the fact that after a vasectomy, some residual sperm which are viable enough to cause pregnancy could remain stored distal to the site of occlusion. The Maternal and Child Health Center of Taiwan documented a case history of a 32-year-old father of 2 who impregnated his wife approximately 38 days, and at least 9 ejaculations, after a successful vasectomy. The patient had no urogenital abnormalities and had an uneventful vasectomy procedure. He resumed intercourse with his wife 8 days after vasectomy and returned for 5 semen tests during the year after vasectomy. The patient's 28-year-old wife had her last menses 24 days after the vasectomy, and pregnancy test 57 days after the vasectomy confirmed the suspicion of pregnancy. Vacuum aspiration terminated the pregnancy 2 days later. There was no doubt or question at all that the patient was his wife's only sexual partner. The authors concluded that based on examination of several thousand postvasectomy semen specimens, the distribution of the biologic limits for residual sperm viability is an asymmetrical distribution skewed to the right, suggesting that the limits may even exceed 38 days for some individuals. Thus physicians should be careful in evaluating a pregnancy which occurs a few months after a successful vasectomy.     

Bronchial asthma,delayed cutaneous response caused by enviromental pollen and fungi (analysis of 250 children)

The metabolic effects of sodium restriction, alone or with thiazide, were studied in 12 healthy subjects, in 24 tetraplegics during the intial 8 months of paralysis (early) and in 16 others during the subsequent period (late). The diuresis caused by both treatments led to more haemoconcentration in early than in late patients. In contrast with the healthy subjects on low sodium, the tetraplegics had a delayed urinary sodium retention and no fall in calciuria. During thiazide, urinary sodium depletion occurred early and the urine calcium fell after 3 days in all tetraplegics. During both treatments, aldosterone and renin increased more in early patients than in the other groups. The clinical implications of inducing dehydration and a sustained stimulation of the renin-angiotensin-aldosterone axis in recently injured tetraplegics with severe orthostatic hypotension are discussed.     

Demand characteristic effects on the subtle and obvious subscales of the MMPI

The MMPI was administered to 40 undergraduate students with 20 subjects asked to imagine that they were applying for a job and 20 subjects asked to imagine that they were applying for psychotherapy. Subjects in the job group dissimulated (faked good) and those in the therapy group malingered (faked bad) as evidenced by differences between the subtle and obvious scores. The combined subtle and obvious score was higher for the psychotherapy group. It was concluded that the subtle, obvious, and combined subtle and obvious scores on the MMPI were a function of the demand characteristics of the testing situation.     

Genetic variability among yellow fever virus 17D substrains

The complete nucleotide sequence of the genome from two yellow fever (YF) virus strains, 17DD and 17D-213 was determined. Comparison of these sequences with those of other YF viruses, including the parental virulent Asibi strain, allowed the identification of 48 nucleotide sequence differences which are 17D strain-specific and potentially related to viral attenuation. Another 43 nucleotide sequence differences were not common to all 17D substrains and are therefore substrain specific. Of the 21 changes between 17DD and Asibi 15 only five led to amino acid substitutions whereas 13 substrain differences common to all 17D-204 substrains produced six amino acid substitutions. Since the exact passage histories of these viruses is known it was possible to calculate, for each strain, the number of accumulated changes per passage. Based on these data the 17DD strain was the most genetically stable virus.     

Nonpeptide cyclic cyanoguanidines as HIV-1 protease inhibitors: synthesis, structure-activity relationships, and X-ray crystal structure studies

Comparison of the high-resolution X-ray structures of the native HIV-1 protease and its complexes with the inhibitors suggested that the enzyme flaps are flexible. The movement at the tip of the flaps could be as large as 7 A. On the basis of this observation, cyclic cyanoguanidines have been designed, synthesized, and evaluated as HIV-1 protease (PR) inhibitors. Cyclic cyanoguanidines were found to be very potent inhibitors of HIV-1 protease. The choice of cyclic cyanoguanidines over cyclic guanidines was based on the reduced basicity of the former. X-ray structure studies of the HIV PR complex with cyclic cyanoguanidine demonstrated that in analogy to cyclic urea, cyclic cyanoguanidines also displace the unique structural water molecule. The structure-activity relationship of the cyclic cyanoguanidines is compared with that of the corresponding cyclic urea analogues. The differences in binding constants of the two series of compounds have been rationalized using high-resolution X-ray structure information.     

Bone morphogenetic protein 6 in skeletal metastases from prostate cancer and other common human malignancies

Prostatic adenocarcinoma commonly metastasizes to bone. Unlike most other bony secondaries, the majority of skeletal prostatic metastases are osteoblastic rather than osteolytic in nature. Several growth factors which are known to stimulate bone formation are expressed in benign and malignant prostate cells, but none has been specifically linked to osteosclerotic metastases. Bone morphogenetic proteins (BMPs) induce ectopic bone formation in vivo. We have reported previously that BMP-6 mRNA and protein are expressed in the majority of primary prostatic carcinomas with established skeletal metastases but rarely in clinically organ-confined tumours. This study examines the expression of BMP-6 mRNA in matched prostatic primary and secondary bony lesions and in isolated skeletal metastases from prostatic adenocarcinomas, as well as other common human malignancies, by in situ hybridization. BMP-6 mRNA was detected in 11 out of 13 bone metastases from prostate carcinoma and in three paired samples of primary prostate carcinoma and matching skeletal metastasis. Weak signals for BMP-6 were also present in 5 out of 17 skeletal deposits from non-prostatic malignancies. BMP-6 mRNA appears to be strongly expressed in prostatic adenocarcinomas, both in the primary tumour and in bone metastases. It is also expressed, though less frequently, in skeletal metastases from other human carcinomas. Our findings suggest that BMP-6 may hold potential as an attractive marker and possible mediator of skeletal metastases, particularly in prostate carcinoma.     

Glucagon-like and insulin-like hormones of the insect neurosecretory system

According to some investigators, trauma is thought to bring about physical changes which produce a coalescence of normally dispersed blood lipids into fat droplets and pulmonary fat embolisms. Lipemia is thought to increase the extent of this embolization. If this theory is correct, intravenously infused labeled oil which is retained in the lungs should be mixed with and diluted by the fat emboli originating from the blood. Radioactive olive oil of known specific activity was slowly administered to a) control rats, b) rats made lipemic by dietary measures, c) severely traumatized rats, and d) traumatized lipemic rats. There was no difference in the specific activity of the oil recovered from the lungs of rats of any group, indicating that no recognizable amount of blood lipids had been added to the experimentally produced emboli.     

Translocation (11;14)(q13;q32) and overexpression of cyclin D1 protein in a CD23-positive low-grade B-cell neoplasm

BACKGROUND: Platinum compounds are the most active drugs in ovarian cancer treatment; cisplatin and carboplatin demonstrated similar efficacies but different toxicity profiles. Paclitaxel combined with cisplatin as first-line treatment improved overall survival when compared to a cisplatin-cyclophosphamide combination, but generated higher rates of neutropenia, febrile neutropenia and neurotoxicity. The paclitaxel-carboplatin combination may be better tolerated than cisplatin-paclitaxel. DESIGN: The objective of the present study was to assess the efficacy and safety of the combination of paclitaxel and carboplatin in previously treated advanced ovarian cancer patients. PATIENTS AND METHODS: During or after platinum-based chemotherapy, 73 patients with progressive advanced epithelial ovarian carcinoma were enrolled to receive every four weeks a three-hour infusion of paclitaxel 175 mg/m2 followed by a 30-minute carboplatin infusion. The carboplatin dose was calculated to obtain the recommended area concentration-versus-time under the curve of 5 mg x ml-1 x min. RESULTS: Toxicity and response could be evaluated for 72 and 62 patients, respectively. Eleven complete and 15 partial responses gave an overall response rate of 42% (95% CI: 30%-54%). Response rates for platinum-refractory patients and those with early (> or = 3 and < 12 months) and late (> 12 months) relapses were 24%, 33% and 70%, respectively. The respective median response duration, the median progression-free survival and median overall survival were 8, 6 and 14 months. Myelosuppression was the most frequent and severe toxicity. Grade 3 and 4 neutropenia occurred, respectively in 30% and 23% of the cycles; 6% of the cycles benefited from medullary growth factors. Only one episode of febrile neutropenia was observed. Grade 3 and 4 thrombocytopenia occurred, respectively during 3% and 1% of the cycles. Alopecia was frequent. Transient peripheral neuropathy developed in 47% of patients but was severe in only one patient. One early death was attributed to progressive disease and possibly to therapy. CONCLUSION: This combined paclitaxel-carboplatin therapy is effective and can be safely administered to ovarian cancer patients who relapse after one or two regimens of platinum-based chemotherapy.