Treatment of resting zone chondrocytes with 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] induces differentiation into a 1,25-(OH)2D3-responsive phenotype characteristic of growth zone chondrocytes.

Vitamin D3 metabolites affect the proliferation and differentiation of cartilage cells. Previous reports have shown that rat costochondral cartilage chondrocytes isolated from the growth zone (GC) respond to 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], whereas those from the resting zone (RC) respond to 24,25-(OH)2D3. The aim of the present study was to determine whether 24,25-(OH)2D3 induces differentiation of RC cells into a 1,25-(OH)2D3-responsive GC phenotype. To do this, confluent, fourth passage RC chondrocytes were pretreated for 24, 36, 48, 72, and 120 h with 10(-7) M 24,25-(OH)2D3. The medium was then replaced with new medium containing 10(-10) to 10(-8) M 1,25-(OH)2D3, and the cells were incubated for an additional 24 h. At harvest, DNA synthesis was measured as a function of [3H]thymidine incorporation; cell maturation was assessed by measuring alkaline phosphatase (ALPase) specific activity. Incorporation of [3H]uridine was used as a general indicator of RNA synthesis. Matrix protein synthesis was assessed by measuring incorporation of [3H]proline into collagenase-digestible protein (CDP) and collagenase-nondigestible protein (NCP) as well as 35SO4 incorporation into proteoglycans. When RC cells were pretreated for 24 h with 24,25-(OH)2D3, they responded like RC cells that had received no pretreatment; further treatment of these cells with 1,25-(OH)2D3 had no effect on ALPase, proteoglycan, or NCP production, but CDP production was inhibited. However, when RC cells were pretreated for 36-120 h with 24,25-(OH)2D3, treatment with 1,25-(OH)2D3 caused a dose-dependent increase in ALPase, CDP, and proteoglycan synthesis, with no effect on NCP production. RC cells pretreated with 1,25-(OH)2D3 responded like RC cells that had not received any pretreatment. To determine whether these responses were specific to chondrocytes in the endochondral pathway, cells were isolated from the xiphoid process, a hyaline cartilage. In these cells, 1,25-(OH)2D3 inhibited ALPase, whereas 36 h of pretreatment with 24,25-(OH)2D3 caused these cells to lose their response to 1,25-(OH)2D3. These results indicate that 24,25-(OH)2D3 can directly regulate the differentiation and maturation of RC chondrocytes into GC chondrocytes, as evidenced by increased responsiveness to 1,25-(OH)2D3. 24,25-(OH)2D3 also promotes differentiation of cells derived from xiphoid cartilage, resulting in the loss of 1,25-(OH)2D3 responsiveness. These observations support the hypothesis that 24,25-(OH)2D3 plays a significant role in cartilage development.

Modulating role of dopamine on anesthetic requirements.

The influence of dopamine on halothane anesthetic requirements was determined in mice. Halothane anesthetic requirement was defined as the minimum anesthetic concentration (MAC) that prevented 50% animals from moving in response to a supramaximal stimulus. Levodopa (L-DOPA) dose-dependently decreased halothane MAC to a maximum of 49% of control; over the same dose range L-DOPA increased striatal dopamine nearly 4-fold. The MAC-reducing effect of L-DOPA was attenuated by selective antagonism of the D2 dopamine receptor with YM-09151-2 while selective blockade of the D1 dopamine receptor with SCH-23390 did not alter L-DOPA's effect on the MAC for halothane. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased striatal dopamine by 82% and increased the MAC for halothane by 27%. Repletion of striatal dopamine with L-DOPA, in MPTP-treated mice, restored the MAC for halothane back to the control state. The regression line derived from the plot of halothane MAC versus striatal dopamine content shows a highly significant correlation between the two variables (r2 = 0.94). These are the first results to suggest that anesthetic requirements can be modulated directly and precisely by increasing or decreasing the content of a single neurotransmitter in the central nervous system.

Complications from prolonged catheterisation prior to prostatectomy.

This paper studies 46 patients with urinary retention who came to prostatic surgery some time later. With prophylactic antibiotics used in cases with urinary infection the risk of surgery is not increased, despite an average period between catheterisation and surgery of one month.

Ectopic ureter in the female causing incontinence.

A case of urinary incontinence is presented in a 12-year-old girl, illustrating the clinical and radiological difficulties in reaching the correct diagnosis.

Fracture of the penis with laceration of the urethra.

Two patients are described with severe injury to the penis sustained during sexual intercourse. The literature is reviewed. A conservative approach to management with suprapubic urinary diversion led to acceptable results.

Ureteroureterostomy for ureteric duplication with one pathological renal segment.

An operation for the management of ureteric duplication with one pathological renal segment is described. A report of 13 cases with 15 duplex systems is presented, showing the merits of ureteroureterostomy as measured against the established procedures.

A New Zealand experience of staghorn calculus surgery.

Sixty-one patients with staghorn calculi who have undergone surgery at the Auckland Department of Urology since 1972 have been reviewed. Maoris have been shown to have a higher disease incidence than Europeans. In those cases followed longer than one year true stone recurrences was 14%. A significant number of patients have developed obstruction in the pelviureteric region, and the reasons for this and possible preventive measures are discussed.

Spermatic cord torsion in the neonate.

Three cases of spermatic cord torsion in neonates are presented. Support is given to the nonoperative management of both the unaffected contralateral testis and late presentation cases.

Some observations on urinary retention and deep hip sepsis following total hip replacement.

A follow-up study was made of 256 hip replacements, performed at Dunedin Hospital by three orthopaedic surgeons in males aged 45 years and over for the six year period beginning 1975 through to the end of 1980. One surgeon (A) had an elaborate management policy designed to reduce postoperative urinary retention and his cases are compared with Surgeon B's whose methods of avoiding urinary retention would be more representative of the majority of orthopaedic surgeons. Analysis was performed of the 20 cases of urinary retention pooled from all three participating surgeons. Also analysed were the 24 cases of epidural anaesthetics in the entire series. Surgeon A had a significantly (P=.045) lower postoperative urinary retention rate of 3.23% compared to surgeon B (12.07%). Analysis of the 20 cases of urinary retention revealed that cases having retention after previous operations and having nothing done about it invariably went into retention again. The retention rate after the 24 epidural anaesthetics was 16.7% and the retention rate after the 232 general anaesthetic cases was 6.9%. This difference was not statistically significant (p=0.10).

The effect of local hypothermia on blood loss during transurethral resection of the prostate.

A prospective trial to investigate the effect of using cold irrigating solution during transurethral resection of the prostate was carried out. A control group of 44 patients was resected using irrigant at room temperature, and a trial group of 49 cases was resected using irrigant cooled to 2 degrees C. Blood loss during surgery was measured to see whether the cold irrigating solution had any effect on this loss. There was a small reduction in blood loss in the cold group, but this reduction was not statistically significant (0.5 greater than P greater than 0.3).

Body temperature changes during transurethral prostatectomy.

A prospective trial was made to investigate the effects of cold irrigating solutions on body temperatures during transurethral resection of the prostate. In a control group of 45 cases, when the irrigating fluids had a mean temperature of 21.9 degree C, there was a significant fall in body temperature from 36 +/- 0.6 degree C to 34.9 +/- 0.7 degree C. In test group A to 48 cases, when the irrigating fluids had a mean temperature of 4.96 degree C, there was a significant fall in body temperature from 36.1 +/- 0.6 degree C to 34.8 +/- 0.9 degree C. In test group B (five cases) when the irrigating fluids had a mean temperature of 10.2 degree C there was a significant fall in body temperature from 36.0 +/- 0.4 to 34.6 +/- 0.8. Comparative analyses between the control group and test group A did not show significant differences in the degrees of cooling in the two groups.

Association between symptomatology and uroflowmetry in benign prostatic hypertrophy.

The symptoms of 128 consecutive patients (mean age 65 years) with benign prostatic hypertrophy were assessed and compared with flowmetry recordings. The 84 patients (65%) with peak flow rates greater than or equal to 2 standard deviations from the mean were considered to have abnormal flowmetry and their symptoms were compared with those of the 44 men with normal peak flows. No significant correlation between peak flow rate and age was found within this group. Symptoms of poor stream, nocturia, post-micturition dribble and nocturnal or full-bladder hesitancy were present in over two-thirds of the whole series. Poor stream, hesitancy and nocturnal or full-bladder hesitancy were found to have significant associations with abnormal flowmetry recordings but also to have a high incidence within the normal flowmetry group. Discriminant analysis was unable to define a symptom complex which would accurately predict those within our group with abnormal peak flows. It was concluded that symptomatology and flowmetry evidence of lower urinary tract obstruction are not associated and subjective and objective evidence must be considered independently in selecting candidates for prostatectomy.

Dexmedetomidine diminishes halothane anesthetic requirements in rats through a postsynaptic alpha 2 adrenergic receptor.

The effect of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole (medetomidine), the alpha 2 adrenergic agonist, on anesthetic requirements was investigated in rats anesthetized with halothane. Halothane MAC was determined before and after either dexmedetomidine (d-enantiomer) or levomedetomidine (l-enantiomer) 10, 30, and 100 micrograms/kg or vehicle ip. There was a dose-dependent decrease in MAC with the d-, but not the l-, stereoisomer. At the highest dose of dexmedetomidine (100 micrograms/kg), halothane could be discontinued for up to 30 min with no response to tail clamping. To determine whether alpha 2 adrenoreceptors mediated this effect of dexmedetomidine on MAC, cohorts of rats were pretreated with idazoxan, 10 mg/kg ip, a highly selective alpha 2 antagonist. This completely prevented the reduction of MAC caused by dexmedetomidine. To determine whether the reduction of MAC caused by dexmedetomidine was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg ip, an opiate antagonist, or 8-phenyltheophylline, 2.5 mg/kg ip, an A1 adenosine antagonist. These two pretreatments did not alter the reduction of MAC by dexmedetomidine. To determine whether postsynaptic mechanisms mediate the anesthetic effect of dexmedetomidine, rats were depleted of central catecholamine stores with either n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine (DSP-4) or reserpine and alpha-methyl-para-tyrosine and MAC was determined before and after each dose of dexmedetomidine. While the catecholamine-depleted rats had a lower basal MAC than the vehicle controls, there was still a profound reduction in halothane MAC after administration of dexmedetomidine. The reduction of MAC by dexmedetomidine was blocked with idazoxan in the catecholamine depleted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging results in an unusual expression of Drosophila heat shock proteins.

We used high-resolution two-dimensional polyacrylamide gel electrophoresis to evaluate the effect of aging on the heat shock response in Drosophila melanogaster. Although the aging process is not well understood at the molecular level, recent observations suggest that quantitative changes in gene expression occur as these fruit flies approach senescence. Such genetic alterations are in accord with our present data, which clearly show marked differences in the synthesis of heat shock proteins between young and old fruit flies. In 10-day-old flies, a heat shock of 20 min results in the expression of 14 new proteins as detectable by two-dimensional electrophoresis of [35S]methionine-labeled polypeptides, whereas identical treatment of 45-day-old flies leads to the expression of at least 50 new or highly up-regulated proteins. In addition, there is also a concomitant increase in the rate of synthesis of a number of the normal proteins in the older animals. Microdensitometric determinations of the low molecular weight heat shock polypeptides on autoradiographs of five age groups revealed that their maximum expression occurs at 47 days for a population of flies with a mean life span of 33.7 days. Moreover, a heat shock effect similar to that observed in senescent flies occurs in young flies fed canavanine, an arginine analogue, before heat shock.

The meatal problem with TUR prostate: the value of post-operative self-dilatation.

In a preliminary retrospective study, we found that 37% of patients about to undergo a transurethral resection of the prostate had an external meatus too small to admit a 26 F resectoscope sheath. In a prospective study, a formal meatotomy was compared with an Otis urethrotomy for patients with a narrow meatus. This study was stopped because 71% of cases having a meatotomy developed strictures compared with 29% having an internal urethrotomy. In a further study of 59 patients, regular self-dilatation of the cut meatus with a plastic spigot was compared with internal urethrotomy of the meatus alone. Seven per cent of cases having self-dilatation developed strictures compared with 34% having internal urethrotomy. It was concluded that in those patients with a narrow external meatus meatotomy should not be carried out, but self-dilatation following internal urethrotomy greatly reduces the incidence of meatal strictures.