Survivin expression in colorectal carcinomas: correlations with clinicopathological parameters and survival.

BACKGROUND: Survivin is a new member of the Inhibitor of apoptosis protein family that has a dual function as a mitotic regulator and apoptosis inhibitor. Survivin is prominently expressed in transformed cell lines and in many human cancers, including colorectal carcinoma. The aim of this study is to investigate the expression of survivin in colorectal carcinomas and its possible associations with clinicopathological parameters and patient survival. MATERIALS AND METHODS: Sections of formalin-fixed paraffin-embedded tissues from 77 colorectal carcinomas were immunohistochemistry stained for survivin. RESULTS: Survivin was mainly detected in the bottom of the glands of normal mucosa with mainly cytoplasmic localization. No survivin expression was found in infiltrating lymphocytes, fibroblasts, smooth muscle cells or neural tissue. Survivin staining was detected in 68/77 (88.3%) colorectal carcinomas. Survivin expression was found to be significantly associated with tumor differentiation (P = 0.02) but not with gender, age or Dukes stage. Survival did not differ according to survivin expression. CONCLUSION: Survivin was found in the majority of colorectal carcinomas, suggesting that its expression is an early event in colorectal carcinogenesis. Its expression is statistically significantly associated with tumor differentiation but not with patient survival.

Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the penis.

BACKGROUND: Cyclin D1 plays an important role in regulating the progression of cells through the G1-phase of the cell cycle. The aim of the study was to investigate the expression of cyclin D1 and Ki-67 in squamous cell carcinomas (SCC) and in some premalignant lesions of the penis and to correlate it with clinicopathological parameters and patient survival. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissues from 21 SCC, 7 lichen sclerosus, 5 condyloma acuminatum and 2 erythoplasia of Queyrat were stained by immunohistochemistry for cyclin D1 and Ki-67. RESULTS: Cyclin D1-positive nuclear staining was overexpressed in 13/21 SCC (61.9%) and in one case of erythoplasia of Queyrat. Strong reactivity for Ki-67 was found in 16 (76.2%) SCC, in 3 condyloma acuminatum and in one case of erythoplasia of Queyrat. A tendency for an association between cyclin D1 expression and tumour differentiation (p = 0.07) but not the level of tumour invasion (p = 0.50) was found. The Ki-67 expression was notably increased with the advance of tumour grade, but the difference did not reach a statistically significant level (p = 0.46). A slight tendency towards a relationship between Ki-67 and cyclin D1 protein expression was observed (p = 0.32). Two patients relapsed and one died from the disease over a median follow-up period of 4.6 years (range 0.1-10.3 years). CONCLUSION: Ki-67 antibody and cyclin D1 overexpression seem to parallel each other, supporting the concept that cyclin D1 serves as a cell cycle activator. Cyclin D1 overexpression may be used as a prognostic factor of poor outcome in penile carcinoma.

Expression of Smad4 and TGF-beta2 in colorectal carcinoma.

BACKGROUND: TGF-beta, a potent natural antiproliferative agent, is believed to play an important role in suppressing tumorigenicity. This effect is mediated through Smad4, a tumour-suppressor gene, at chromosome 18q21, which affects gene transcription and controls cell growth. The aim of the study was to investigate the expression of Smad4 and TGF-beta2 in colorectal carcinomas and to correlate them with pathological parameters and patient survival. MATERIALS AND METHODS: Formalin-fixed paraffin-embedded tissue from 49 cases of colon carcinoma was stained by immunohistochemistry for TGF-beta2 and Smad4 protein. RESULTS: Smad4 nuclear and cytoplasmic staining was absent in 9/49 (18.3%) or reduced in 18/49 (36. 7%) colorectal carcinoma, while in the remaining 22 (44.8%) Smad4 expression comparable with colonic mucosa was observed. TGF-P2 cytoplasmic staining was expressed in all cases and was overexpressed in 24/49 (48.9%) carcinoma. A statistically significant correlation was found between Smad4 expression and tumour grade (p =0.02) and between TGF-beta2 expression and Dukes' stage (p=0.03). A slight tendency for a relationship between Smad4 and TGF-beta2 (p=0.25) was also observed. No statistically significant relationship between the above markers and survival was detected. CONCLUSION: In poorly-differentiated carcinoma, Smad4 protein expression was retained and may be linked to TGF-beta2 overexpression, due to the activation or deregulation of the TGF-fl signalling pathway. Inactivation of the TGF-beta gene occurs at an early stage of colorectal carcinogenesis, while inactivation of Smad4 is probably a late event.

Plasma and urine elastase alpha-1-proteinase inhibitor levels in neonatal urinary tract infection.

OBJECTIVE: To examine whether plasma or urine elastase alpha(1)-proteinase inhibitor (E-alpha(1)-PI) levels could be used as a diagnostic marker of urinary tract infection (UTI) in neonates. SUBJECTS AND METHODS: Plasma and urine E-alpha(1)-PI levels were measured by immunoassay in 23 neonates with UTI at the time of admission and 72 h after the onset of treatment and in 10 'normal' neonates (i.e. with trivial problems). Additionally E-alpha(1)-PI plasma levels were measured in 15 neonates with septicemia. RESULTS: E-alpha(1)-PI plasma levels did not differ between normal neonates and those with UTI. Urine E-alpha(1)-PI levels were significantly higher in neonates with UTI on admission compared to normal neonates. A significant decrease in urine E-alpha(1)-PI levels was noticed 72 h after the onset of treatment in all but 2 neonates in whom infection persisted. In this study, we have found that the urine E-alpha(1)-PI concentration at a cutoff level of 48 microg/l had a sensitivity of 83%, a specificity of 90%, a positive predictive value of 95% and a negative predictive value of 69% for the diagnosis of neonatal UTI. CONCLUSION: Elevated levels of E-alpha(1)-PI in urine seem to be a useful tool for the diagnosis of UTI in neonates (even in those that have already been started on antibiotics) and possibly a valuable marker for early recognition of treatment failure.

Late recurrence of herpes simplex virus meningoencephalitis in two infants.

UNLABELLED: Two infants with recurrence of herpes simplex virus (HSV) encephalitis are reported. Both patients developed HSV encephalitis during their neonatal period and were treated with iv acyclovir. Long-term oral acyclovir prophylaxis was given thereafter. At the age of 8 and 11 months respectively, both babies, while under oral acyclovir prophylaxis, presented a second episode of HSV encephalitis. An inadequate dose of suppressive oral acyclovir therapy may be responsible for the recurrence of encephalitis in these two babies. CONCLUSION: The present observations emphasise the need for very long follow-up of any infant who has suffered from neonatal herpes simplex virus encephalitis and the need for careful prospective controlled studies in order to define the appropriate treatment regimen (initial plus prophylaxis) for neonates with herpes simplex virus infections.

Rectal-axillary temperature difference in febrile and afebrile infants and children.

The rectal-axillary temperature difference (R-A) was measured in the morning, at midday, and in the afternoon on 1,519 occasions in 1,149 children from birth to 5 years old. Of these, 302 children were febrile (rectal temperature > or = 38 degrees C) and 847 were afebrile. A wide range in R-A was found for each individual in both groups. The magnitude of this difference was not associated with sex or age. In febrile children, the R-A was significantly greater (P < .0001) at the apparent onset of fever (1.04 +/- 0.25 degrees C) than later, when fever had been present for at least two hours (0.53 +/- 0.22 degrees C). These findings indicate that it is impossible to find a standard number by which to convert axillary to rectal temperature or vice versa. Furthermore axillary temperature may be relatively low or even "normal" despite an elevated rectal temperature at the onset of fever.

Blood-brain barrier permeability in "healthy" infected and stressed neonates.

The assessment of the blood-brain barrier permeability (BBBP) showed that BBBP values were higher in stressed neonates and those with bacterial meningitis than in "healthy" infants or neonates with aseptic meningitis. The BBBP determination may be helpful in differentiating bacterial from aseptic meningitis; the high BBBP should be considered in the management of stressed neonates.

Rectal-skin temperature difference in septicaemic newborn infants.

Serial skin (sole) and rectal temperatures were simultaneously taken from 55 healthy and 26 septicaemic newborn infants to find out prospectively whether septicaemic newborn infants have any thermoregulatory reaction to the septicaemia, and whether regular temperature measurements could help in the early diagnosis of septicaemia. The septicaemic infants were divided into three groups: the first comprised eight feverish infants, the second 11 with normal temperatures who were in relatively good clinical condition, and the third seven with normal temperatures who were in poor clinical condition. All 55 healthy babies had rectal temperatures of less than 37.8 degrees C and a mean rectal-sole temperature difference of 2.5 degrees C. The first group of septicaemic infants had rectal temperatures over 37.8 degrees C and a high mean temperature difference of 6.9 degrees C, whereas the second group had rectal temperatures less than 37.8 degrees C and a mean temperature difference of 4.7 degrees C. Infants of the third group had a low rectal temperature and a low mean temperature difference (1.1 degrees C). We conclude that septicaemic newborn infants show an adequate thermoregulatory reaction, which is reflected by a widening of the rectal-sole temperature difference of more than 3.5 degrees C, except for those who are critically ill, who lose this ability. In view of these results infants with normal temperatures but with a rectal-sole temperature difference of more than 3.5 degrees C should be suspected of septicaemia and investigated thoroughly.

Comparative study of Harvey-ras oncogene expression with conventional clinicopathologic parameters of breast cancer.

We have previously examined the expression of the Harvey-ras (Ha-ras) oncogene related transcripts in human malignant breast tumors and in their respective normal tissue [Spandidos and Agnantis, Anticancer Res. 4: 269-272, 1984]. Our results revealed a significant elevation of Ha-ras transcripts in malignant compared to normal tissue. In the present follow-up study we have examined the relationship of Ha-ras oncogene expression to the various clinicopathological parameters of these tumors. Although elevated expression was observed in all breast tumors as compared to their respective normal breast tissue there was no correlation with the tumor stage as defined by the TNM system. However, several correlations between Ha-ras oncogene expression and histologic parameters were found and comparisons of the mean value of Ha-ras oncogene expression with the parameters examined showed the following: the stellate tumor margin and the larger tumor size had the lowest mean value; the infiltrating duct histologic type had the highest mean value; the mean value was lower in the presence of lymphocytic infiltration in the tumor; a higher mean value was obtained in cases with lymph node metastases.

Hearing loss in low-birth-weight infants.

The hearing of 98 perinatal intensive care survivors with a mean birth weight of 1,540 g was assessed at a mean age of 6 1/2 years. They represented 73% of the long-term survivors with birth weights of 1,800 g or less who had been cared for in our neonatal unit during the three-year period 1971 through 1973. Nine of the 98 infants had sensorineural hearing loss, and 14 had exudative otitis media. During their neonatal period, the infants with hearing loss experienced more frequent apneic attacks, hyperbilirubinemia (serum bilirubin level, greater than 14 mg/dL), and hypothermia compared with their healthy counterparts. There was no evidence that the duration of stay in the incubator or the use of stay in the incubator or the use of ototoxic drugs had affected the hearing of these low-birth-weight infants.

Hyperglycemia in very low birth weight infants: a common iatrogenic problem.

From a total of 36 very low birth weight infants (less then 1200 g) admitted to our neonatal unit during an 18-month period, 7 were fed per os while the remaining 29 received, during the first 4 days of life, parenteral glucose infusion either as a supplement to oral feedings (n: 11) or as the only source of fluids (n: 18). Among these 29 infants 21 (72%) manifested hyperglycemia (blood glucose greater than 125 mg/dl). On the contrary none of the 7 infants receiving oral feedings exclusively manifested hyperglycemia. Hyperglycemia was related to high rates of glucose infusion (greater then 0.4 g/kg/hr). These data attest to the fragile nature of glucose metabolism in infants of very low birth weight.

A nursery outbreak of Serratia marcescens infection. Evidence of a single source of contamination.

An outbreak of Serratia marcescens infection occurred in a special neonatal unit. The epidemic involved seven newborns, one of whom died. Contaminated hand-washing brushes were implicated in the epidemic; their removal resulted in a dramatic elimination of the infection.

Noise pollution in neonatal units: a potential health hazard.

Hospital noise levels were measured for four consecutive days every two hours throughout the day in a neonatal intensive care unit (NICU), a normal nursery room and inside infant incubators when the latter were associated with different types of life-support equipment. There was a difference in the noise level between normal nursery and NICU, whereas a considerable increase of noise was recorded when the infant received supplemental oxygen, was under ventilator or when an air compressor was in operation. High noise levels were equally the same both in a.m. and p.m. hours in the NICU. As many high risk infants spend a long time in a NICU, there is an urgent need for further evaluation of noise levels and their effect on the outcome of infants.

Effect of prolonged illumination (phototherapy) on concentrations of luteinizing hormone in human infants.

Concentrations of luteinizing hormone in the serums of human neonates were altered when the neonates were exposed to prolonged, intense illumination (phototherapy) with their eyes covered. Concentrations decreased after 48 to 72 hours of exposure, increased 6 to 9 days after phototherapy, and subsequently returned to levels similar to those of controls. These data suggest that light may affect pituitary-gonadal function in the human neonate.

Cardiac complications after vaccination for smallpox.

A case of severe myocardial damage 8 days after smallpox vaccination is described in a 6-year-old boy. A huge embolus overriding the bifurcation of the aorta complicated the disease and was removed surgically. Attention is called to the rapid recovery of this patient, which may be attributed to the use of massive doses of antivaccinia gamma globulin.