Clinical features of patients suffering from Streptococcus milleri infections--a retrospective analysis. We examined the clinical records of patients from whom S. milleri was isolated at Kyushu University Hospital from January 1987 through December 1988. Sixty-one patients were treated in 64 episodes with drainage or antibiotics. Oral and nasopharyngeal infections were observed in 27 cases, intrathoracic infections in 13, urogenital infections in 8, intraabdominal infections in 6 and skin and subcutaneous infections in 6. Except for acute bronchitis and urogenital infections, all of them were suppurative. As to underlying diseases, 21 patients had malignancies and 6 had diabetes mellitus. Leukocytopenia was not observed in any of the patients. S. milleri can be eradicated by treatment but it is sometimes replaced by other organisms. However, considering its tendency to cause suppurative infections, its pathogenic significance should be taken into account and patients should undergo surgical drainage combined with antibiotic therapy.


Corneal sensitivity during and outside attacks of cluster headache. Corneal sensitivity has been studied in cluster headache (n = 38) and controls (n = 16). The patients were studied either during remission (n = 20), interparoxysmally in a bout (n = 17), or during attacks (spontaneously occurring attacks (n = 5) and nitroglycerin-provoked attacks (n = 6). For the measurements, a Cochet-Bonnet esthesiometer was utilized. This esthesiometer has a 6 cm long, adjustable nylon monofilament, which can be reduced in length by 0.5 cm at a time, the length of the filament determining the pressure exerted onto the corneal surface. All controls sensed the pressure at 6.0 cm filament length. In 5 cluster headache patients (remission, n = 4; cluster period, n = 1) a slight reduction in corneal sensitivity was found. No statistical difference was, however, found between any of the groups tested, and there was no asymmetry as far as averages were concerned.


[Clinicopathological study on the proliferation and differentiation of laryngeal carcinoma and dysplasia]. It is important to examine the proliferative activity of cells in the laryngeal carcinoma and dysplasia for the decision of the clinical treatment and the presumption of the prognosis. I studied here the proliferative activity with three indications, such as the measurement of nuclear DNA contents by flow cytometry, immunohistochemistry of Proliferating Cell Nuclear Antigen (PCNA) and intake of bromodeoxyuridine (BrdU). Furthermore, I compared the proliferative activity with cellular differentiation, which was investigated by immunohistochemistry of involucrin, a marker of human mature suprabasal squamous epithelia. Flow cytometric DNA analysis was performed in 69 patients of laryngeal carcinoma and in 15 patients of dysplasia. In laryngeal carcinoma, 41 cases (59%) had DNA aneuploid pattern, and in dysplasia, 6 cases (40%) represented aneuploid group, and 27% and 11% per 1 hour in diploid group, respectively. The mean of DNA Index (DI) was 1.21 in the carcinoma and 1.13 in the dysplasia. In the cases of recurrent carcinoma and transformed carcinoma, aneuploid pattern was predominant and DI was high. I performed double staining of BrdU and involucrin in these cases. The former is an index of cellular proliferation and the latter is a marker of the differentiation, as described above. These two markers showed reciprocal relationship in normal squamous cell layers, dysplasia and many areas of squamous cell carcinoma. But, some cells of the carcinoma in advanced stage represented concomitantly positive result in these two markers. This finding suggests the biological disorder in these carcinoma cells and requires the follow-up examination of these cases.


Effects of ibogaine on naloxone-precipitated withdrawal in morphine-dependent mice. In naive mice, ibogaine at a tremorigenic dose (30 mg/kg, ip), did not produce antinociception but did potentiate the antinociceptive potency of morphine in the tail-flick test. In morphine-dependent mice, ibogaine did not eliminate withdrawal symptoms but significantly increased the number of repetitive vertical jumps induced by naloxone, whatever the duration of the chronic morphine treatment. By comparison, repetitive jumping induced by alpha-napthoxyacetic acid (alpha-NOAA), a non-convulsant drug which induced jumping without affecting other morphine-withdrawal signs, was not significantly modified by ibogaine. These results indicate that while acute antinociceptive effects of morphine are modulated by ibogaine, this drug, shown to alleviate opiate dependence in man, does not attenuate in mice opioid withdrawal manifestations.


Electrocortical power spectrum changes induced by microinfusion of corticotropin-releasing factor into the locus coeruleus in rats. Rat corticotropin-releasing factor (CRF) microinfused unilaterally or bilaterally into the locus coeruleus (LC) of awake, chronically cannulated rats produced a dose-dependent ECoG desynchronization and behavioral activation. ECoG spectra analysis revealed a significant decrease of total voltage power and of 0.25-3 and 3-6 Hz frequency bands. These effects were prevented by a pretreatment into the same site with alpha-hCRF, a selective antagonist at CRF receptors and by alprazolam, a benzodiazepine derivative. In conclusion, the present results indicate that CRF produces its behavioral and ECoG activating effects by interaction with specific receptors located on LC neurons.


Inhibition of [3H] gamma-aminobutyric acid release from guinea-pig hippocampal synaptosomes by serotonergic agents. We studied the effects of (m-trifluoromethyl-phenyl)piperazine (TFMPP) and quipazine on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes loaded with [3H]GABA.TFMPP and quipazine inhibited the K(+)-evoked release of [3H]GABA dose-dependently (IC50 = 153 and 123 microM, respectively). Serotonergic antagonists such as methiothepin (0.1, 0.3 and 1 microM), ketanserin (0.1, 0.3 and 1 microM), dihydroergotamine (0.1 microM), metergoline (0.1 and 0.3 microM), methysergide (0.3 microM), propranolol (1 microM) and yohimbine (1 microM) did not significantly alter the inhibitory effect of TFMPP on [3H]GABA release suggesting that neither 5-HT1 nor 5-HT2 receptors are involved in this process. By contrast, the effect of TFMPP was diminished by selective 5-HT3 receptor antagonist: MDL 72222 (0.3 microM), tropisetron (0.3 and 1 microM), ondansetron (0.3 microM) and metoclopramide (1 microM). Tropisetron (1 microM) and ondansetron (0.3 microM) also inhibited significantly the quipazine effect whereas methiothepin (1 microM), dihydroergotamine (0.1 microM), yohimbine (1 microM) and ketanserin (1 microM) were ineffective on the quipazine inhibition of [3H]GABA release. Our results show a serotonergic modulatory effect on the K(+)-evoked [3H]GABA release from guinea-pig hippocampal synaptosomes by receptors which are neither 5-HT1, 5-HT2 or 5-HT4. They appear to be pharmacologically related to the 5-HT3 type but different from the 5-HT3 ionic channel receptors.


Cardiovascular effects of TENS: heart rate variability and plethysmographic wave evaluation in a group of normal subjects. Transcutaneous electrical nerve stimulation (TENS) is generally used in controlling pain. Side effects are not frequent, but sometimes do happen. Among these, automatic disturbances have been described. The purpose of the investigation was to study high frequency TENS effects on heart rate variability and the plethysmographic wave. Results showed no change in heart rate variability parameters (Standard Deviation, Mean Square Successive Difference) despite an increase in R-R interval, while a decrease in the amplitude of the plethysmographic wave was observed. This study seems to point out that high frequency TENS does not modify the neural control to the heart while a sympathominetic effect is shown on the peripheral plethysmographic wave.


Sneddon's syndrome and renal carcinoma. Case report. A patient with Sneddon's syndrome in association with renal neoplasm is discussed. The association has not been reported before and raises questions concerning the pathogenesis of vascular proliferation in Sneddon's syndrome.


Treatment with growth hormone-releasing hormone (GHRH) 1-44 in children with idiopathic growth hormone deficiency: a randomized double-blind dose-effect study. The GHRH European Multicenter Study (GEMS) Group. One hundred and eleven pre-pubertal children (70 boys, 41 girls, aged 2.5 to 14.3 years) with growth failure (height 2 SD below the mean for chronological age (CA) and height velocity (HV) below the 10th percentile for bone age) due to idiopathic growth hormone deficiency (peak plasma GH < 20 mUI/1 to two standard provocative tests) were treated with GHRH 1-44 NH2. Patient stratification in two classes was performed according to body weight; in each class, patients were randomly allocated to one of seven GHRH doses, from 30 to 300 micrograms/day. GHRH was injected subcutaneously, every evening, for six months in a double-blind fashion. No relationship was found between the absolute or incremental HV during treatment and the dose (range from 1.3-23.1 micrograms/kg/day) of GHRH. However, HV (cm/year) increased from 3.8 +/- 0.1 (mean +/- SEM) before treatment to 6 +/- 0.2 during six months treatment and 47 patients (42%) increased their HV up to at least the mean normal HV for bone age (catch-up growth). Low titer antibodies to GHRH were found in 19 patients (17.1%) at six months; no adverse effect was observed. Our results suggest that patients showing catch-up growth were older, had a height closer to the mean for chronological age and a slower pre-treatment height velocity. Failure to demonstrate a relationship between GHRH dose and changes in growth velocity might be explained by the combination of a placebo effect, insufficient frequency of GHRH administration and heterogeneity of the population.


Lack of effect of isradipine on cyclosporin pharmacokinetics. The influence of isradipine as a long acting form (IcazR LP 5 mg) on cyclosporin pharmacokinetics was studied in six hypertensive renal transplant patients (mean age 37 yrs; mean body weight 62 kg). These patients received a mean daily cyclosporin dose of 307 mg in two equal intakes. Isradipine was orally administered once a day at a dose of 5 mg before the morning cyclosporin intake. Cyclosporin kinetics was assessed over a 0-12-h period, the day before (D-1) and 13 days (D+13) after isradipine treatment. Whole blood concentrations of cyclosporin were determined by radioimmunoassay (RIA) using the SandimmuneR-RIA kit (specific and non-specific monoclonal antibodies). Area under the blood concentration-time curve (AUC), the maximum blood concentration (Cmax) and the time to reach Cmax (Tmax) on D-1 and D+13 were not significantly different whatever the specificity of the RIA method. For example, the mean AUC +/- sd values were 5,247 +/- 2,255 (D-1) vs 5,317 +/- 1,675 (D+13) microgram.1(-1).h for the specific and 20,905 +/- 8,317 vs 19,327 +/- 5,758 microgram.1(-1).h for the non-specific determinations. Therefore, the pharmacokinetics of cyclosporin is not influenced by co-administration of isradipine at a therapeutic dosage. Moreover, the clinical results show that isradipine treatment was effective after 13 days administration (mean systolic blood pressure 132 vs 158 mm Hg, P < 0.05 and mean diastolic blood pressure 77 vs 93 mm Hg, P < 0.05 in supine position), and well tolerated throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)


Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers. The purpose of the present study was to determine whether erdosteine and its metabolites (substances containing thiol groups) can prevent the alteration of the chemotactic function of polymorphonuclear cells (PMN) from peripheral blood induced by cigarette smoke of eight healthy non-smoking volunteers, when incubated in vitro before smoke exposure, and whether oral treatment with erdosteine (900 mg/day) for two weeks might restore the chemotaxis of PMN, either from eight healthy or from 16 chronic bronchitic smokers. The chemotactic stimuli in vitro were casein, lipopolysaccharides (LPS), and formyl-methionyl-leucyl-phenyalanine (FMLP). The results of the study in vitro have confirmed that PMN from non-smoking volunteers shows a reduced chemotactic responsiveness when exposed in vitro to smoke. This can be partially prevented in a dose-related manner by pre-incubation with erdosteine, its metabolites, cysteine, and glutathione (metabolites I and II being at least 10 times more active than the intact substance and the known biological standards also containing thiol groups). The experiment on PMN from healthy smokers (in a double-blind crossover design versus placebo) has indicated that the chemotaxis can be improved only after treatment with erdosteine. The same observation has been made in the experiment on PMN from smokers affected by chronic bronchitis (in a double-blind design versus placebo with two distinct groups). In these patients the phagocytic and bactericidal activities of PMN were not affected by the smoke and therefore, neither one was influenced by erdosteine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Malotilate completely inhibits CCl4-induced liver cirrhosis in rats: biochemical and morphological analysis. Malotilate, diisopropyl 1,3-dithiol-2-ylidenemalonate, is a relatively recently synthesized hepatotrophic chemical substance. Its inhibitory effect on rat liver cirrhosis induced by carbon tetrachloride (CCl4) was biochemically and morphologically investigated for 10 weeks, since this chemical had been reported to suppress liver damage caused by CCl4 or in vitro collagenogenesis of human fibroblasts. Concomitant administration of malotilate with CCl4 completely suppressed liver cell necrosis and markedly inhibited fatty change of hepatocytes in the first three weeks of the experiment. During the six to ten weeks of the experimental period, liver cirrhosis was perfectly inhibited by malotilate. Previously established liver cirrhosis, however, could not be normalized by malotilate treatment. Precise mechanism of the inhibitory effect of malotilate on liver cirrhosis is not elucidated, but this substance is clearly effective for preventing liver cell damage and/or liver cirrhosis caused by CCl4.


Emotion and identification of environmental sounds and electroencephalographic activity. Eight environmental sounds, i.e., playing the harp, cuckoo's song, sound of the waves, cock's crow, noise of the subway, alarm of a clock, sound of a dentist's drill, scratching of the blackboard, and their temporally reverse sounds were presented for 20 sec to 16 college students in a sound-attenuated chamber. The subjects were requested to estimate the degree of pleasantness-unpleasantness and confidence in identifying each sound 10 sec after presentation. Electroencephalography was recorded at C3, C4, O1 and O2 (International 10-20 system), and the mean EEG powers of delta, theta, alpha-1, alpha-2, beta-1 and beta-2 bands during the sound presentations were computed by a signal processor. The results were as follows: 1) Even when the loudness and frequency component of the sounds were equivalent, there was big difference in pleasantness-unpleasantness estimation among the environmental sounds. 2) Inaccuracy in identifying the sounds presented backwards neutralized the pleasantness-unpleasantness estimation. 3) Powers of theta and low frequency alpha bands were higher during presentation of the pleasant sounds than during presentation of the unpleasant sounds. 4) Alpha activity was more closely related with subjective confidence in sound identification than with pleasantness-unpleasantness estimation of sound. These findings suggest that pleasantness-unpleasantness estimation of environmental sounds depends not only on their loudness level or frequency component but on the accuracy in sound identification and that modification of sound identification may be useful in alleviating the environment noise problem. Alpha activity seems to be closely related to the recognition of sound, but further research is needed on EEG activity in the relationship between the emotional state and sound identification.


Optic atrophy, sensorineural hearing loss and polyneuropathy--a case of sporadic Rosenberg-Chutorian syndrome. We report on a 41-year-old woman with slowly progressive motor dominant polyneuropathy, optic atrophy and sensorineural deafness, but without any known familial feature. These neurological manifestations were in accordance with the syndrome reported by Rosenberg and Chutorian in 1967 (Rosenberg-Chutorian syndrome), a unique form of Charcot-Marie-Tooth disease. The syndrome was first reported to be autosomal dominant in trait, but subsequently recessive forms and sporadic ones have also been described. Nerve biopsy and neurophysiological studies including electromyography, nerve conduction velocities, somatosensory evoked potentials, auditory brainstem responses, and visual evoked potentials revealed the axonopathic involvement of the central nervous system as well as the peripheral nervous system. Since neurophysiological aspects of this particular syndrome have not been well studied, these results would provide some insight into the understanding of this disorder.


Growth-hormone-binding protein in patients with acromegaly. The present study was undertaken to investigate the possible regulatory effect of chronic exposure to human growth hormone (hGH), in patients with acromegaly, on growth-hormone-binding protein (GH-BP). Nineteen patients with active acromegaly, before, during or after treatment, comprised the subjects of this study. Serum GH was measured by radioimmunoassay and GH-BP by a binding assay with dextran-coated charcoal separation. The specific binding of [125I]hGH (1 ng) obtained with 50 microliters serum was expressed as a percentage of total cpm. To evaluate the impact of the lower GH-BP on GH activity, we studied the effect of acromegalic serum on hGH displacement of [125I]hGH binding to GH receptors in rabbit liver membranes. Compared to normal controls (11.43 +/- 0.37%), the acromegalic patients had low serum levels of GH-BP (5.45 +/- 0.40%; p < 0.001), which correlated negatively with serum GH levels (p < 0.01). In 7 patients, GH-BP normalized within 2-3 months of successful therapy. The lower GH-BP was due to a reduction in binding capacity, whereas binding affinity remained unchanged. Acromegalic serum, with its low GH-BP, resulted in a shift to the left of the GH displacement curve when compared with normal human sera: IC50 values were 7.47 +/- 0.29 and 11.19 +/- 0.84 ng (p < 0.02) for acromegalic and normal human sera, respectively. We conclude that acromegaly is characterized by low levels of GH-BP due to a decrease in serum-binding capacity. The decrease in GH-BP may render the acromegalic serum GH relatively more active in the GH receptor assay.


Bone turnover in overt and subclinical hyperthyroidism due to autonomous thyroid adenoma. Parameters of bone turnover were measured in 20 premenopausal women affected by autonomous thyroid adenoma: 7 patients were suffering from overt hyperthyroidism with raised values of free thyroid hormones; 13 were clinically euthyroid and had normal values of free thyroid hormones. In all cases serum TSH concentrations were below the lower normal limit of our laboratory (< 0.4 mU/l). Eleven healthy premenopausal women were studied as a control group. Patients with overt hyperthyroidism disclosed a significant enhancement of both bone resorption (increased serum calcium and urinary excretion of hydroxyproline) and bone formation (increased serum levels of osteocalcin and alkaline phosphatase) when compared both to controls and to patients with subclinical hyperthyroidism. No significant alterations of bone metabolism parameters were found in patients with subclinical hyperthyroidism in comparison with controls. Therefore, in premenopausal women affected by autonomous thyroid adenoma the bone turnover appeared to be significantly increased when the serum values of free thyroid hormones were raised in the group of patients with overt hyperthyroidism.


Insulin activity: stimulatory effects of cinnamon and brewer's yeast as influenced by albumin. Cinnamon and Brewer's yeast extracts have been shown to potentiate the action of insulin in isolated adipocytes. In this study, isolated rat epididymal adipocytes were used to evaluate the influence of bovine serum albumin on insulin activity as affected by cinnamon and Brewer's yeast extracts. Albumin at 0.01-0.1% decreased the insulin stimulatory effects of cinnamon from 11.8- to 5.3-fold and 2% albumin decreased this effect to near control levels. Conversely, the insulin-enhancing properties of Brewer's yeast remained low in the presence of less than 0.25% albumin but subsequently increased 2.8-, 4.8- and 5.6-fold in the presence of 0.25, 0.50 and 1.0% albumin, respectively. In the absence of added insulin, increased activity of the insulin-stimulated utilization of glucose by both extracts was observed but only Brewer's yeast extract displayed additive effects when tested at higher insulin levels. Due to the inhibitory and enhancing effects of albumin on the insulin activity of cinnamon and Brewer's yeast, respectively, it is suggested that the effects of albumin be assessed when evaluating the insulin-enhancing effects of other substances using isolated adipocytes.


Pulses of oxytocin in the cerebrospinal fluid of rhesus monkeys. Cerebrospinal fluid (CSF) samples were collected at frequent intervals (every 10-15 min) to determine if oxytocin pulses were present in the CSF of monkeys. Temporary indwelling subarachnoid catheters, with the tip of the catheter at the T12-L1 subarachnoid space, were placed in 4 nonlactating and 3 lactating (4 months post partum) female monkeys. Monkeys were maintained on jacket/tether/swivel systems in a constant photoperiod (07.00-19.00 h). CSF was continuously withdrawn at a rate of 1.2 ml/h by peristaltic pump, and CSF was collected in 15-min fractions (from 3 lactating monkeys and 1 nonlactating monkey) or in 10-min fractions (from the other 3 nonlactating monkeys) using a fraction collector. CSF oxytocin was measured by radioimmunoassay. Pulses of oxytocin were analyzed using the computerized Pulsar pulse detection algorithm. A pulsatile pattern of oxytocin concentrations was found in the CSF of lactating and nonlactating monkeys. The ultradian pulses of oxytocin were superimposed upon the diurnal rhythm of oxytocin in CSF. We conclude that frequent sampling of CSF provides a way to monitor moment-to-moment changes in central nervous system concentrations of oxytocin in primates.


The sole presence of the testis-determining region of the Y chromosome (SRY) in 46,XX patients is associated with phenotypic variability. Four cases of XX patients with testis development are reported. The aim of this study was to describe their clinical features and to see if there was any relationship between phenotypes and the presence of Y material. Several human Y-derived sequences including the SRY probe were used to analyze the DNA of the patients. Yp material including the pseudo-autosomal region and SRY was detected. The cases reported in this study confirm that XX true hermaphrodites cannot be distinguished from XX males on the basis of their genotypes. There is no relationship between clinical and anatomical phenotypes and the presence of Y material. SRY does not warrant a complete and normal testis differentiation. Although similar in some features with Klinefelter's syndrome patients, XX males exhibit specific clinical manifestations due to the lack of Y-specific genes.


Evolutionary origins of intercellular communication systems: implications for mammalian biology. Traditionally, the two major systems of intercellular communication (i.e. the nervous and endocrine systems) were considered separate functional and anatomical entities. Recent studies have provided evidence that the biochemical elements of these systems have common early phylogenetic origins and have suggested that, with the exception of their anatomical diversity, all the systems of intercellular communication are biochemically similar. On the basis of these findings, we suggest that the overlaps between the nervous and endocrine systems, the widespread tissue production of hormones, and other phenomena are now more easily understood.


Role of insulin-like growth factors and growth hormone in reversing catabolic states. The insulin-like growth factors (IGFs) mediate the anabolic effects of growth hormone or protein synthesis in muscle and skeletal tissues. Administering growth hormone to normal volunteers who have been made catabolic by caloric restriction improves the nitrogen balance. The studies described illustrate that administration of somatomedin-C (IGF-I) to catabolic normal volunteers also results in improved nitrogen balance and, unlike growth hormone, does not induce insulin resistance. Growth hormone was anabolic in patients with severe chronic obstructive lung disease and resulted in improved chest wall muscle strength. Both IGF-I and growth hormone have the potential to improve muscle mass and function in patients who are catabolic due to the severity of their underlying disease state.


Growth hormone actions on fat distribution and metabolism. The secretion of growth hormone (GH) and the mass and distribution of body fat are linked through a complex series of interactions. There is increasing evidence that a GH/fat cycle exists and that elements of this cycle may possess regulatory functions. The essential elements of the cycle are: (1) GH-deficient individuals are often obese and lose body fat when they are treated; GH is lipolytic in vitro and causes an acute release of free fatty acids (FFA) when administered in vivo; (3) circulating FFA inhibit the pituitary release of GH by most secretagogues, including growth hormone releasing hormone, and (4) the obese state is characterized by a defect in GH release which can be reversed by weight loss.


The effects of human growth hormone and prednisone on whole body estimates of protein metabolism. Human growth hormone (GH) increases estimates of whole body protein synthesis, but has little effect on the rates of proteolysis either post-absorptively or when absorption occurs during a meal. In contrast to insulin, GH stimulates protein synthesis in skeletal muscle tissue. Prednisone in high doses induces protein catabolism and has been used as a controlled model for catabolic illness. Prednisone increases the rates of proteolysis and amino acid oxidation, but has little effect on estimates of protein synthesis. The administration of high doses of GH together with prednisone prevents the protein catabolic effects of prednisone alone. Thus, GH may provide a new management strategy in patients with significant protein catabolic conditions.


Growth hormone and insulin interactions. Insulin and glucose clamp techniques were used to investigate insulin action and insulin secretion during childhood. Preliminary results suggest that growth hormone (GH) therapy leads to changes in glucose, amino acid and insulin responses that are qualitatively similar to those observed during puberty. Furthermore, the insulin resistance normally seen during puberty may be restricted to peripheral glucose metabolism. In patients with Turner's syndrome, data indicate that there is an increase in the glucose-stimulated insulin response which is exaggerated by GH treatment.


Gender and sexual orientation in relation to hypothalamic structures. Animal experiments have provided evidence for the presence of sex differences from the synaptic level up to behaviour. Although sex differences in the human brain may have been presumed implicitly since the days of Aristotle, research on the presence of functional and structural sex differences of the human brain started only relatively recently. The most conspicuous sex difference in the mammalian brain was described by Gorski et al. [1978] in the preoptic area (POA) of the rat hypothalamus. We found that the volume of a putative homologue of this sexually dimorphic nucleus (SDN) in the adult human hypothalamus was more than twice as large in men as in women and contained about twice as many cells. Recently a similar sex difference and volume has been described for the human bed nucleus of the stria terminalis and 'interstitial nuclei of the hypothalamus' (INAH). Sexual differentiation of the hypothalamus was generally believed to take place between 4 and 7 months of gestation. A life span study on the SDN of more than 100 subjects revealed, however, that only after the age of 2-4 years postnatally sexual differentiation becomes manifest by a decrease in volume and cell number in the female SDN. If sexual differentiation of the brain indeed takes place postnatally, not only chemical and hormonal factors may influence this process but also social factors. A prominent theory on the development of sexual orientation is that it develops as a result of an interaction between the developing brain and sex hormones. According to Dörner's hypothesis, male homosexuals have a female differentiation of the hypothalamus. This hypothesis was not supported by our observations on the SDN. Neither the SDN volume nor the cell number in the hypothalamus of homosexual men differed from that of heterosexual men. However, a difference in SCN cell number was observed in relation to sexual orientation. The volume and cell number of the SCN of homosexual men was twice as large as that of a reference group. During development, the SCN volume and cell counts reach peak values around 13-16 months after birth. At this age the SCN contains about the same number of cells as the SCN of adult male homosexuals, whereas in the reference group the cell numbers subsequently decline to the adult value, which is about 35% of the peak value.(ABSTRACT TRUNCATED AT 400 WORDS)


Genetic determinants of testis development in normal and abnormal individuals. A candidate for the male sex determining gene 2 has recently been isolated. This gene, named SRY, has an expression profile consistent with a role in testis determination, is mutated in some XY females, and causes female to male sex reversal in transgenic mice. The cloning of this gene should facilitate the characterization of other genes in the testis determining pathway.


Differentiation of the fetal gonad.

Differentiation of the fetal gonad. Gonadal differentiation may be divided into four stages: pregonadal, indifferent, primary sex differentiation, and secondary sex differentiation. Sertoli cells appear at 6-7 weeks and Leydig cells differentiate at 8 weeks, but in ovaries, primary sex differentiation occurs much later. Testosterone secretion peaks at 12-16 weeks causing male secondary sex development together with the appearance of anti-Müllerian hormone. Fetal testis is able to synthesize and secrete inhibins. Lower circulating luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in male than in female fetuses at midgestation suggest that the fetal pituitary is already responsive to the gonadal hormones. Placental human chorionic gonadotrophin may regulate testosterone synthesis at midgestation, and both LH and FSH are likely to have some regulatory effect on fetal gonads during the last third of gestation.


Anti-müllerian hormone and Sertoli cell function. Anti-müllerian hormone (AMH) is a glycoprotein that is produced by immature Sertoli cells and is responsible for the regression of müllerian ducts in male fetuses. It is a useful marker of testicular function in children, when anorchia is suspected and in intersex states. In the persistent müllerian duct syndrome, both AMH-positive and AMH-negative forms have been reported. In three cases of the latter, a mutation of the AMH gene is thought to have been responsible for the condition.


Male pseudohermaphroditism: clinical management, diagnosis and treatment. Male pseudohermaphroditism (MPH) is a disorder of sexual differentiation whereby the external genitalia are at variance with a male karyotype and the presence of testes. Abnormalities of Leydig cell function are an important cause of MPH, but postnatal age must be considered when interpreting the testosterone response when HCG stimulation is used as a diagnostic test. Androgen insensitivity is also a common cause of MPH; the specific defect in androgen receptor function is currently the subject of intense study, using a combination of biochemical assays and molecular analysis of the androgen receptor gene. The treatment of MPH is influenced by genital tissue responsiveness to androgens and the technical complexity of reconstructive surgical procedures. There is a need for information on the outcome of MPH treatment regarding pubertal development, sexual performance and fertility.


Syndromes and genital dysmorphology.

Syndromes and genital dysmorphology. External and internal genitalia can be malformed by genetic and environmental factors without involvement of sex chromosomes or fetal gonads. Thus, genital dysmorphology may be part of many syndromes of various etiology, such as monogenetic disorders, autosomal chromosomal abnormalities and non-random malformation syndromes of unknown etiology. Genital dysmorphology may also occur as a result of teratogenic effects following maternal ingestion of synthetic progestins. The genital manifestations in all these syndromes occur more commonly in males than in females. Penetrance and expression of these abnormalities tend to show great variability.


Autoimmune polyglandular syndromes.

Autoimmune polyglandular syndromes. Autoimmune polyglandular syndromes originally defined by Blizzard, Maclaren and Neufeld were classified into three constellations based on the clinical clustering of the various component diseases. Type I and type II are reasonably well circumscribed entities with type III being an ill-defined group. The autoimmune nature of these diseases has been based on the presence of lymphocytic infiltration in the affected gland, organ specific autoantibodies in the serum, cellular immune defects and an association with the HLA DR/DQ genes or immune response genes. Autoantibodies to the various endocrine and non-endocrine tissues not only offer a diagnostic clue to the autoimmune nature of diseases but also can be used to identify asymptomatic individuals who are at risk of developing other component diseases of the syndrome. In this review the clinical and serological spectrum of type I and II APS will be discussed.


Factors that affect depth perception in stereoscopic displays. This study investigated several factors that affect depth perception in stereoscopic displays: half-image separation magnitude, separation direction (crossed vs. uncrossed), viewing distance, stimulus size, and exposure duration. The depth perceived under various combinations of levels of these factors was compared with depth predicted by the geometry of stereopsis. Perceived depth in the crossed-separation direction was frequently close to predictions, such that increases in separation and viewing distance produced appropriate increases in perceived depth. Depth in the uncrossed direction was frequently less than that predicted, especially for small stimuli presented at a long viewing distance, with a large half-image separation, and/or with a brief duration. Thus depth in both crossed and uncrossed directions equaled predictions only for large stimuli exposed for a long duration.


Human stereopsis.

Human stereopsis. This paper reviews much of the basic literature on stereopsis for the purpose of providing information about the ability of humans to utilize stereoscopic information under operational conditions. This review is organized around five functional topics that may be important for the design of many stereoscopic display systems: geometry of stereoscopic depth perception, visual persistence, perceptual interaction among stereoscopic stimuli, neurophysiology of stereopsis, and theoretical considerations. The paper concludes with the presentation of several basic ideas related to the design of stereoscopic displays.


Time stress and the processing of visual displays. Selecting the appropriate display format for time-constrained tasks is the focus of the research presented in this paper. The effect of time stress on operator performance was assessed by manipulating the time available to process the display. Twenty people were trained as operators and instructed to identify the state of a system using either a digital display or a polygon display. Participants were required to reach a prespecified criterion in training and were then tested under time-constrained conditions. Time constraints were set at 100%, 50%, and 25% of each person's mean unpaced response times obtained during training. Results showed that response to the time constrained conditions was significantly affected by uncertainty and the type of display format. Discussion focuses on the effects of time stress on performance and the selection of displays for time-constrained tasks.


Cervical cancer in India--strategy for control. The available information on the incidence of cancers by site in India have indicated that of incidence of cancer of uterine cervix among women is by far the highest compared to other sites in women. The epidemiology of cervical cancer has been studied extensively in India and in other countries. The majority of factors related to cervical cancer are associated with sexual behaviour. The available evidence for control of cervical cancer is through secondary prevention, namely--early detection through Pap smear. In the present communication the alternative strategies with secondary prevention for control of cervical cancer is worked out. Taking into consideration the number of cervical cancer cases saved, number of woman years saved and the cost aspects the strategy at present for India should be to provide one life time screening for women at the age of 45 years.


Primary tracheo oesophageal puncture our initial experience. Our initial experience of 9 primary tracheo oesophageal punctures with Blom Singer prosthesis is reported. Patient selection was based on motivation, intelligence and socioeconomic status. Excellent speech resulted in 7 out of 9 patients (77%), with 2 failures (23%). There were no major complications. The results are encouraging, but a larger study is required to determine the role of this procedure in our conditions.


Cancer profile in western Rajasthan.

Cancer profile in western Rajasthan. A retrospective study of malignancy was conducted in the arid region of Western Rajasthan over a period of five years (1984 to 1988) to determine the frequencies of various malignancies. This was the region where India's first nuclear explosion took place in 1974. During this period 2662 new cancer cases were recorded. In males, Oropharyngeal and Hypopharyngeal malignancies topped the list. Males had an overall higher incidence than females (1.28:1). Most of the cases were between 31 years and 60 years with male peak at 60 years and female at 50 years. In females, cancer of the cervix formed the largest group followed by Breast cancer. A comparatively high rate of skin, urinary bladder, bone malignancy, lymphoma and leukaemia was observed in this region. Limited investigational facilities, lack of trained personnel, tough working condition, extremes of temperature, long distances in the desert region, with associated poverty, illiteracy and ignorance were some of the factors responsible for majority of the patients presenting in advanced stages.


Induction chemotherapy in non-metastatic high grade osteo sarcomas--results of pilot study at Cancer Institute (WIA), Madras. Twelve patients with high grade osteosarcomas of the extremities were treated with two cycles of induction chemotherapy using adriamycin and cis-platinum and sandwich radiation between the two cycles (4000 rads). Ten patients underwent amputation or disarticulation, two patients had wide excision followed by endoprosthesis. The specimen was assessed for grade of necrosis. The Disease Free Survival at a minimum follow-up period of 26 months and median follow-up period of 35.5%. All the five patients who developed distant metastases had shown only a grade I necrosis in the tumour.


Primary subglottic carcinoma.

Primary subglottic carcinoma. Primary subglottic carcinoma is rare with a uniformly poor prognosis. We present our experience of eight such cases treated over a period of ten years. One patient had a mucoepidermoid carcinoma while the rest had a squamous cell carcinoma. A combination of surgery and radiotherapy was employed in five cases, while one case each underwent radiotherapy only, surgery only and salvage surgery following radical irradiation. Three cases died of locoregional failure within a year. The remaining five patients have been disease-free for six months to 3.5 years.


The dose time relationship in the radiotherapy of carcinoma of the cervix--application of CRE formalism. A retrospective analysis of 291 patients with cancer of the uterine cervix treated with a combination of external and intracavitary radiotherapy was carried out. Patients were either treated with 45 Gy in 20 fractions by five fractions per week or with 42 Gy in 14 fractions by three fractions per week or with 42 Gy in 14 fractions by three fraction per week schedule by external radiotherapy. For brachytherapy the total dose was 24 to 32 Gy at a dose rate of 1.4 to 2.2 Gy per hour. Complication were correlated with total CRE values for point A (CRE TA) and for rectum CRE TR. Correlations of CRE TA with overall complication rate (p value < 0.05) and rectal complication rate (p value < 0.01) were excellent. Lack of correlation was observed between CRETR and overall complication rate (p value > 0.1) as well as rectal complication rate (p value > 0.1). In order to limit Grade II and III rectal and bladder complications to acceptable level, in combined external and intracavitary treatments, CRETA value of less than 2500 reu is suggested.


Pure red cell aplasia and non-Hodgkin's lymphoma: a case report and brief literature review. Pure red cell aplasia associated with lymphoproliferative malignancies other than thymoma is an uncommon occurrence. In the present paper we report a rare case of nodular non-Hodgkin's lymphoma with pure red cell aplasia who presented with symptoms related to anemia rather than the lymphoma and responded well to combination chemotherapy.


Primary lymphoma of breast--report of six cases and review of literature. Six patients of primary lymphoma of breast are presented. All our patients were female with median age of 46 years. Combination chemotherapy was the mainstay of treatment in all the patients. Five patients achieved complete remission of which two relapsed, one had a distant relapse and the other was local. Patient with distant relapse expired after a follow-up of 224 months whereas the one with local recurrence was well controlled with radiotherapy only. The role of combination chemotherapy to decrease the distant relapse and thereby mortality is discussed.


Gastric transposition & deltopectoral flap for peristomal recurrence following total laryngectomy--a case report. Stomal recurrence following laryngectomy presents a difficult problem with an incidence of 8.3-15%. Wide excision of the recurrence with mediastinal dissection, although the operation of choice,m is technically demanding and has a high morbidity and mortality. We recommend a technically easier procedure for reconstruction after palliative excision and present a case to illustrate it.


Computed tomography evaluation of esophageal carcinoma. Forty patients of histologically proven esophageal carcinoma were subjected to computed tomography (CT) with the objective to assess its reliability in preoperative evaluation of these patients. The findings were confirmed on surgery in twenty five of these patients, thought to be resectable. Bronchoscopy was performed to evaluate bronchial tree in cases of tumor of upper and middle third of esophagus. CT was found to be sensitive in predicting the location and size of tumor, in assessing invasion of tracheo-bronchial tree, spread to liver, celiac and left gastric nodes. However, it was not successful in picking up metastatic spread to local periesophageal nodes in five cases and celiac in one case. The study concluded CT should be carried out for preoperative evaluation of esophageal carcinoma to select operable cases and avoid unnecessary radicle surgery in advanced cases.


Total leukocyte acid phosphatase and its isoenzymes in patients with leukemia. Leukocyte acid phosphatase and its isoenzyme composition was studied in leukemic patients to determine the specificity of different isoenzymes in leukemic leukocytes. It was found that leukocyte acid phosphatase content is significantly increased in ALL, AML, and CML patients, while CLL patients had decreased levels of acid phosphatase. The distribution and intensity of leukocyte ACP isoenzymes vary in respective leukemic condition. Thus isoenzyme 'O' was predominant in AML and CML, while isoenzymes 1, 2 and 3 predominated in ALL. The lack of predominance of isoenzyme 3 was a feature in CLL patients. It was concluded that the isoenzyme patterns, though promising, presented inconclusive picture for diagnosis purpose and further studies on immunochemical characteristics of these isoenzymes are warranted to ascertain their cell specificity.


Malignant systemic mastocytosis.

Malignant systemic mastocytosis. Malignant Systemic Mastocytosis is a very rare condition. Only about less than 40 well documented cases have been reported as per the available literature. The paper presents the case report of a 54 year old male patient who presented with huge hepatosplenomegaly and abdominal lymphadenopathy. Splenectomy specimen was 17 x 16 x 10 cm size with cut surface studded with numerous tiny 1-2 mm nodules. Histologic sections of spleen showed extensive mast cell (typical and atypical) infiltrates. Liver biopsy and abdominal lymphnode biopsy specimens and bone marrow smears also showed similar infiltration by mast cells. Special stains done for non-specific esterase and chloracetate esterase showed strong positivity for mast cells. The results of immunohistochemical and electron microscopic studies are also presented.


Morbidity & mortality following craniofacial resections. A seven year experience with twenty patients undergoing the craniofacial approach for excision of tumours of the paranasal sinus and orbit is presented. Results indicate a low postoperative morbidity and mortality with excellent cosmesis. Good palliation is achieved in the presence of extensive disease, while large tumours which would have been considered inaccessible can be resected. Its advantage recommend it as the treatment of choice for tumours of the orbit and paranasal sinuses.


Neck metastasis from an occult primary--the Kidwai experience. This study highlights our treatment policy in 26 cases of epidermoid metastatic carcinoma in the neck from a primary deemed occult after exhaustive examination of the Upper Aero-digestive Tract (UADT). Planned Radical Neck Dissection (RND) and post-operative radiotherapy (RT) has been the favoured approach in all neck nodes deemed resectable and a loco-regional control rate of 64% was obtaining using this combined modality approach. Pre-operative RT was utilised in three cases with nodal disease of borderline resectability and loco-regional control was achieved in one case. Three cases of massive neck metastasis initially deemed unrectable became amenable to surgical salvage after Radical RT with concurrently administered chemotherapy. Only one of these remained disease free. Overall loco-regional control rate of 55 per cent could be achieved in 20 evaluable patients followed up for two years--three years (mean 30.5 months). Regional failures were noted in 25 per cent of patients while distant spread occurred in 15 per cent, thus accounting for an overall failure rate of 40 per cent. Manifest primaries were documented in 20 per cent, half of which could be salvaged and successfully controlled.


Choroidal metastasis from primary adenocarcinoma of the esophagus--a case report. Primary adenocarcinoma of the esophagus is uncommon and the incidence in the middle third is rare, accounting for about 0.7 percent to 1.5 percent. Metastasis of carcinoma to the eye is a rare occurrence. We report here a case of primary adenocarcinoma of the middle third of the esophagus with choroidal metastasis.


Epidermoid cyst of the brain stem--a case report. Epidermoid cysts occurring within the brain stem are extremely rare and only nine such cases are reported in the literature. In this report, we report a case of Intrapontine epidermoid cyst in a young female patient.


Tumour induced osteomalacia: a report of two cases. A disease of defective matrix synthesis? Tumour induced hypophosphataemic osteomalacia or rickets is a well delineated clinical entity. There is confusion, however, about the nomenclature and classification of the associated tumours. The tumour factor responsible for the biochemical abnormalities has also not been identified. We report here two cases: one, a 43 year old male with a soft tissue tumour in the left vastus medialis, and the other, a 25 year old female with a soft tissue tumour in the right anterior axillary fold. Reversal of biochemical abnormalities and clinical improvement occurred after removal of the tumour in both cases. Both tumours showed unusual morphology characterised by spindle cell component, large vascular spaces, osteoclast-like giant cells, calcification and ossification. The tumour in the second patient was benign, while the nature of the tumour in the first patient was debated. We speculate that defective matrix may be the cause of unusual histology of the tumours, and also the source of the phosphaturic factor.


Extranodal sinus histiocytosis with massive lymphadenopathy--a case report. Sinus histiocytosis with massive lymphadenopathy involving organs other than the lymph nodes is a rare event. A case of SIIML presenting with multiple skin and subcutaneous nodules and multiple osteolytic lesions is described. A search of the Indian literature revealed many cases of nodal SIIML, but none of the reported cases had prominent extranodal involvement.


Malignant 'multinodular' oncocytoma of parotid gland--a case report and literature review. The pathological findings in a multinodular malignant oncocytoma of the parotid gland in a male 62 years of age, with tumour infiltration into the adjacent skin and skeletal muscle and with regional lymph node metastasis is presented.


Detection of rabies virus in different tissues of experimentally infected mice at preclinical and postclinical stages of the disease. Rabies fixed virus (CVS) was passaged 10 times in mice by intramuscular (im) route followed by experimental inoculation of the titrated virus in 4 groups of mice with the dose of 0.1 ml of 1000 mouse (LD50 0.03 ml) using intracerebral (ic), intravenous (iv), intramuscular (im), intraocular (io), and intranasal (in) routes respectively. No marked variation in clinical signs due to variation of routes could be detected. Involvement of brain with io route could be detected even in preclinical stage. Although the virus could be detected in the postclinical stage in all the tissues under study (brain, skin, salivary gland and corneal impression), with io and ic routes spread of the virus was observed in comparatively higher concentrations.


Prevention of development of tolerance and dependence to opiate in mice by BR-16A (Mentat), a herbal psychotropic preparation. Chronic treatment with BR-16A (20-500 mg/kg) followed by saline on days 1 to 9 failed to produce any significant change in tail-flick latency from the saline-pretreated group in mice. Repeated administration of BR-16A(20-500 mg/kg) for 9 days however, attenuated the development of tolerance to the analgesic effect of morphine (10 mg/kg). BR-16A (20-500 mg/kg) also suppressed, in a dose-dependent manner, the development of morphine dependence as assessed by naloxone (2 mg/kg)-precipitated withdrawal on day 10 of testing.


Effects of plant extract Centella asiatica (Linn.) on cold restraint stress ulcer in rats. Extract of C. asiatica (Linn.) inhibited significantly gastric ulceration induced by cold and restraint stress (CRS) in Charles-Foster rats, Antiulcer activity of plant extract was compared with famotidine (H2-antagonist) and sodium valproate (anti-epileptic). Plant extract, formotidine and sodium valproate showed a dose dependent reduction of gastric ulceration. Plant extract increased brain GABA level which was also dose dependent. Pretreatment with bicuculline methiodide (specific GABAA-antagonist) at the dose level of 0.5 mg/kg im, reversed the antiulcerogenic activity of both plant extract and sodium valproate. Bicuculline as such did not induce gastric ulceration in normal rat.


Stage specific effect during one seminiferous epithelial cycle following ethylene glycol monomethyl ether exposure in rats. Stage specific effect of single oral dose (500 mg/kg body wt) of ethylene glycol monomethyl ether (EGME) was characterised during one cycle of seminiferous epithelium in rats. Maximum peritubular membrane damage and germinal epithelial distortion were observed at stages IX-XII. Cell death occurred during conversion of zygotene to pachytene spermatocytes (stage XIII) and between dividing spermatocytes and step I spermatids (stage late XIII-XIV). Profound effect was noted during first meiotic division than during second meiotic division. Presence of multinucleated secondary spermatocytes indicated cytokinesis arrest. The spermatogenesis was delayed and consequently frequency of tubules at stages I-VIII was reduced by day 10. Many of the tubules were devoid of round spermatids on day 12. Possibly, EGME (or it's metabolite) distorted the barrier system at stages IX-XIV and damaged the cells mostly at stages XII-early XIV.


In vitro study of rat uterus after chronic formaldehyde exposure. To measure cholinergic, adrenergic and tryptaminergic receptor activity of formaldehyde (HCHO) in rat uterus, albino rats were treated with 5 and 10 mg/kg, ip HCHO for 30 days. Acetylcholine (ACh) in doses 1.33, 2 and 3 micrograms/ml produced mild to moderate contraction of isolated rat uterus in control group. HCHO had no effect on isolated rat uterus per se, however it reduced ACh and carbachol induced contraction and presence of adrenaline influences in respect of ACh and carbachol activity. Adrenaline per se had no effect in control preparations, but reduced carbachol induced contraction. Propranolol had no effect on rat uterus; but its presence in the bathing medium increased activity of adrenaline. 5-Hydroxytryptamine (5-HT) had no effect of its own on isolated rat uterus but its presence in the bathing medium enhanced contractions of carbachol and oxytocin.


Iron bioavailability from Spirulina platensis, whole egg and whole wheat. Bioavailability of iron from Spirulina was assessed in comparison with whole egg, whole wheat and standard ferrous sulphate using haemoglobin depletion repletion assay. Haemoglobin regeneration efficiency of Spirulina and whole egg was similar and significantly higher than that of whole wheat. The absorption of iron from Spirulina was significantly lower than that of ferrous sulphate and whole egg but significantly greater than that from whole wheat.


Effect of centchroman and tamoxifen on protein patterns of fallopian tubes of rhesus monkeys, Macaca mulatta. To study the effect of centchroman and tamoxifen on estrogen-dependent proteins of fallopian tubes of rhesus monkey, these antiestrogens were given with and without estradiol to ovariectomized monkeys. In absence of estradiol, both the compounds induced the synthesis of 130 and 95 K proteins. Concentration of 85 K protein was also increased markedly. These compounds, however, suppressed the estrogen stimulated synthesis of 130 K protein when administered with estradiol. The results show that both centchroman and tamoxifen possess estrogen agonistic as well as antagonistic properties and 130 K protein can be used as a marker protein to study estrogen action and for screening of antiestrogenic compounds in a primate model.


Effect of diethylcarbamazine on acetylcholine and gamma amino butyric acid in Setaria digitata. In vitro studies on the effect of neurotransmitter amino acids and amines on the motility of S. digitata showed that acetylcholine (Ach) had a stimulatory and gama amino butyric acid (GABA) an inhibitory effect on the parasite. When the worms were incubated in different concentrations of diethylcarbamazine there was a significant dose related increase in the level of Ach, and the level of GABA remained unchanged. Inhibition of acetylcholine esterase activity by diethylcarbamazine caused the accumulation of Ach in the synapses resulting in receptor desensitization and after a momentary stimulation causes paralysis of the parasite.


An improvised method of laboratory colonization of Phlebotomus papatasi, the vector of cutaneous leishmaniasis. A cyclic colony of P. papatasi was successfully established, using wild caught females. The major obstacle in the colonization was infestation of fungus, which was solved when bentonite, a dehydrant was mixed in the larval diet i.e., powdered and sterilized faecal pellets of rabbit. The average duration of development from egg to adult was 46.41 +/- 3.26 days. Females readily engorged on mouse, which was kept immobilized inside restrainer cages Majority of the fed females laid viable eggs, when confined in improvised styro-foam humidity chambers and survived after oviposition. In this process a stable, cyclic colony was established and it is now in F39 generation.


Characteristics of monoclonal antibodies against porcine zona pellucida-3 and their functional relevance. Seven monoclonal antibodies (MAs) against 55 kDa glycoprotein family of porcine zona pellucida (ZP3) reacting with either ZP3 alpha (MA-7, MA-27, MA-28) or ZP3 beta (MA-1, MA-2, MA-11, MA-30) have been described. MA-1, -2, -27, -28 and -30 do not recognize carbohydrate determinants as shown by their reactivity to the deglycosylated (DG) ZP3 alpha and ZP3 beta. Indirect immunoperoxidase studies showed that all MAs reacted with zona pellucida from porcine and monkey ovaries. Only MA-1 and -27 reacted with ZP from rabbit ovary as well, while none of the MAs recognised mouse ZP, MA-7, -11, -27, -28 and -30 inhibited in vitro, the zona lysis by trypsin as well as the binding of ZP3 to sperm membrane vesicle as investigated by ELISA.


Patterns of inhibin and FSH localization in endometrium of baboon (Papio anubis) during menstrual cycle and early pregnancy. Immunoreactive 10.5 KDa moiety of inhibin and hFSH was present in the baboon endometrium during menstrual cycle, early pregnancy and in castrated animals treated with steroid hormones, estrogen and/or progesterone. Endometrial differences during the menstrual cycle altered the intensity of immunostaining of inhibin and FSH. Maximum staining was observed in late luteal phase for both the hormones. In early pregnancy (35th day), the conceptus increased the staining for inhibin in the adjoining endometrial glands. Treatment of castrated animals with steroids for 14 days caused increased staining for inhibin. Maximum staining was observed when treated with estradiol or progesterone, whereas combination of estrogen and progesterone treatment decreased the staining reaction. In conclusion, both inhibin and FSH were localized in baboon endometrium and were under the influence of estrogen and progesterone.


Seminal inhibin--prospects for immunocontraception. Passive immunization of adult rats, hamsters and marmosets with rabbit anti-seminal inhibin resulted in complete or partial block of fertility. The antiserum treatment presumably neutralized endogenous inhibin resulting in an unopposed rise in circulating FSH. This probably led to a refractoriness of the testes to FSH resulting in complete spermatogenic arrest. Nevertheless, there was no change in the mating behaviour of the animals. The antibodies also affected the epididymal spermatozoa by causing large scale agglutination.


Antifertility effects in rats actively immunized with 80 kDa human semen glycoprotein. A 80 kDa human sperm antigen has been identified using the serum of an infertile woman having circulating antisperm antibodies. The antigen was then purified to homogeneity by gel permeation chromatography using HPLC (protein PAK-125 column) system and on FPLC (superose-12 column) system. The antigen was found to be a glycoprotein. The antigen was mainly localized in the postacrosomal region of the human sperm, while it was localized in the head region of the rat sperm as demonstrated by immunofluorescent staining. The presence of this antigen was also demonstrated in the human prostate and endometrium and in the rat testis; epididymis and the prostate by immunocytochemical staining. The purified protein upon active immunization in female rats caused infertility in 100 percent animals. While in male rats it caused infertility in 90 percent animals. On morphometric analysis of testicular tissue it was observed that there was no significant change in spermatogonia and spermatocytes, but significant decrease in spermatids and sperm number as well as daily sperm production in the immunized male rats. The epididymal spermatozoa were markedly reduced in number and were largely found to be agglutinated. The results suggest that 80 kDa human sperm antigen appears to be a suitable candidate for immunocontraception both in male and female.


Dual regulatory action of prostatic inhibin (10.7 kDa) on DNA synthesis. Present studies deal with the role of inhibin in proliferation and growth. The effect of inhibin on incorporation of 3H-thymidine in prostatic DNA in vivo as well as by NRK-49F and Balb/c3T3 cell lines in vitro, was investigated. Also studied the immunocytochemical localization of inhibin in normally proliferating and differentiated tissues of human prostate and endometrium. The in vivo studies revealed a suppression of 3H-thymidine uptake both in ventral (33%) and dorsolateral (26%) lobes of rat prostate. Interestingly, the histology of inhibin treated rat prostate manifested amidst the epithelial lining, an appearance of apoptotic bodies which are considered to be indicative of cell death. Further, the immunocytochemical studies for localization of inhibin showed intense staining in the differentiated human prostate and endometrium as compared to the respective proliferative tissues. Is inhibin kept suppressed in these proliferating tissues, because it is antiproliferative? The present in vitro experiments demonstrated that, at low inhibin concentrations, the incorporation of 3H-thymidine is stimulated while at higher doses it is suppressed. Thus, it is clear that prostatic inhibin seems to have a concentration-dependent dual role in the regulation of DNA synthesis.


Interrelationship between ovine follicular fluid inhibin and serum albumin. Ovine follicular fluid inhibin (oFF-I) as isolated in this laboratory, proved to be a monomeric protein (M(r).65 kDa). It was found to share very many of the physico-chemical characteristics of ovine serum albumin (oSA)-such as molecular size, iso-electric point, N-terminal aminoacid, finger-print patterns following enzymatic or cyanogen bromide cleavage, as well as binding of estradiol-17 beta and tryptophan. Furthermore, an antiserum containing polyclonal antibodies to oSA showed perfect cross-reaction with oFF-I. Nevertheless, oFF-I is distinct and different from oSA, as would be evident from the data reported here. Of the two proteins, oFF-I alone is capable of suppressing pituitary FSH output in a dose-dependent manner. Secondly, an antiserum containing polyclonal antibodies against Fraction-S2, a partially purified, biologically active fragment (M(r): 30-40 kDa)-derived from oFF-I, cross-reacted with the 65 kDa inhibin, but did not recognize oSA. Finally, the CD-spectra of the two proteins, when examined as a function of pH, show characteristic differences.


Kinetics of spermatogenesis in megachiropteran bat, Rousettus leschenaulti (Desmarset): seminiferous epithelial cycle, frequency of stages, spermatogonial renewal and germ cell degeneration. The paper describes in detail the cytomorphology of different types of germ cells, the 10 typical cellular associations or stages of the cycle of seminiferous epithelium (CSE), frequency of appearance of these stages, pattern of spermatogonial stem cell renewal and per cent degeneration of various germ cells in R. leschenaulti. Of the 14 steps of spermiogenesis (stained with PAS-haematoxylin) the first 10 were associated with the stages I-X, whereas, the remaining were found in association with one of the first six stages. The frequency of appearance of the various stages ranged from 3.84% (stage V) to 19.84% (stage I). These observations indicate that stage V is of shortest duration and stage I is of the longest duration in the bat. Five types of spermatogonia (A1, A2, A3, In and B) were identified based on their shape, size and nuclear morphology. Type A spermatogonia are oval with a large nucleus containing 1 or 2 nucleoli. The chromatin showed progressive condensation from A1 to A3 so that the latter appeared darkest among all the A type spermatogonia. The In type derived from A3 are smaller but appear darker than A3 due to heterochromatin crusts along the inner border of the nucleus. The B type spermatogonia derived from In are round and possess single nucleolus. The B type spermatogonia divided mitotically before entering meiosis or the actual production of the primary spermatocytes. The various spermatogonia divided mitotically at fixed stages of the cycle giving rise to their next generations.(ABSTRACT TRUNCATED AT 250 WORDS)


Amphiphilic and hydrophilic domains of human sperm membrane antigens recognized by immunoinfertile sera. Selected sera from married couples with immunological infertility were used to identify antigens on hydrophilic and amphiphilic domains of human sperm membrane. Out of eight sera, six recognized proteins from the hydrophilic as well as amphiphilic regions of the sperm membrane. Sera were either reactive to acrosome or to equator and tail of human sperms in indirect immunofluorescence assay.


Antifertility investigations on the crude chloroform extract of Carica papaya Linn. seeds in male albino rats. Crude chloroform extract of C. papaya seeds (5 mg/animal/day, po, for 20, 40 and 60 days) was investigated for contraceptive efficacy and related side effects in male albino rats. The crude extract reduced fertility to zero per cent by 40 to 60 days of treatment. Suppression of cauda epididymal sperm motility was the most pronounced effect of the drug administration. Scanning electron microscopic observations revealed treatment induced abnormalities in sperms. Cauda epididymal and testicular sperm counts decreased following treatment. Clinical parameters did not show any alterations. Results suggest that the contraceptive effects of chloroform extract of papaya seeds are mainly post-testicular in nature without influencing toxicological profile and libido of the animals.


Maturation-dependent goat epididymal sperm autoagglutination and its inhibition by a glycoprotein factor. The maturing goat epididymal spermatozoa were isolated from different segments of epididymis and these cells dispersed in a modified Ringer's solution, were incubated at 37 degrees C for 60 min to evaluate their autoagglutination efficacy. Distal corpus-epididymal spermatozoa specifically showed high order of head-to-head autoagglutination property whereas all other sperm cells did not show any detectable aggregation. The goat epididymal plasma has been shown to possess an anti-agglutinin that markedly inhibits sperm agglutination phenomenon and also dissociates the cells from the sperm clusters. Epididymal plasma is the most potent source of the anti-agglutinin which is a heat-stable specific glycoprotein. Like the autoagglutination phenomenon, the initiation of sperm forward progression also starts in the distal-corpus epididymis. The temporal correlation of these two events suggests that sperm autoagglutination may be a prerequisite for the induction of flagellar motility during the epididymal maturity of male gametes.


Effect of efferentiectomy on enzymes of glycolytic pathway, HMP pathway and TCA cycle in epididymis and vas deferens of rhesus monkey. The importance of exocrine secretions of testis in the regulation of energy metabolism of the epididymis and vas deferens was examined in rhesus monkeys by performing efferentiectomy. At autopsy the epididymis was divided into initial segment, caput, corpus and cauda portions to make an account of regional differences, if any. Eleven enzymes of glycolysis, two key enzymes of HMP pathway and seven enzymes of TCA cycle were assayed in the epididymal segments and vas deferens of control (intact) and experimental (efferentiectomised for 90 days) monkeys. The results indicate that while anaerobic energy metabolism (glycolysis and HMP pathway) is sensitive to efferentiectomy chiefly in the proximal regions of epididymis, the oxidative pathway (TCA cycle) is dependent on testicular exocrine secretions throughout the length of epididymis, as well as in the vas deferens. Since all androgen-sensitive enzymes do not regress after efferentiectomy, it is suggested that unidentified exocrine factors of testis may have role in regulating energy metabolism in the epididymis and vas deferens.


Role of prolactin on epididymal glycoprotein metabolism in matured monkeys, Macaca radiata: specific activities of glycosyltransferases and glycosidases. Impact of altered serum prolactin status on enzymes involved in glycoprotein metabolism in epididymal tissue of matured monkeys was studied. Hyperprolactinemia (ovine prolactin-250 micrograms/kg body weight/day for 30 days) significantly inhibited the specific activities of dolichylphosphate mannosyl transferase, dolichylphosphate glucosyl transferase and galactosyl transferase, in the epididymal tissues. However, it had an enhanced effect on epididymal glycosidases such as beta-galactosidase, beta-N-acetyl glucosaminidase, beta-N-acetyl galactosaminidase, alpha-mannosidase and alpha-L-fucosidase. Hypoprolactinemia (bromocriptine mesylate-1-mg/kg body weight/day for 30 days) on other hand had no significant effect on the specific activities of both, glycosyltransferases and glycosidases, in the epididymal tissues. The results suggest that hyperprolactinemia inhibits epididymal glycoprotein metabolism by impairing the incorporation of oligosaccharide units into proteins with enhanced degradation. This may have adverse effect on events leading to sperm maturation in epididymal environment.


Serum and semen levels of immunoreactive prolactin, LH and FSH in normospermic, oligospermic and azoospermic men with obstructive infertility prior to and after vasoepididymostomy. Attempts were made to validate RIA for prolactin (PRL), LH and FSH in semen from normospermic, oligospermic and azoospermic subjects. The RIA used to measure PRL and LH in semen fulfilled the criteria of reliability, whereas low levels of FSH in semen precluded the validation of FSH assay in semen. Semen levels of PRL and LH were significantly (P < 0.05) higher than serum levels in all groups of subjects investigated. Semen levels of FSH in azoospermic men after vasoepididymostomy (VEA), were significantly (P < 0.05) higher compared to azoospermic men prior to surgery. Serum levels of PRL were significantly higher (P < 0.05) in normospermic men compared to oligospermic and azoospermic men prior to and after surgery. Semen levels of PRL in normospermic men were comparable with oligospermic and azoospermic subjects prior to and after surgery. Serum levels of LH in oligospermic and azoospermic men who did not undergo surgery and in men reporting oligospermia after VEA were comparable to normospermic subjects but in men showing azoospermia post surgically, serum LH levels were significantly (P < 0.005) elevated. Semen levels of LH in men reporting azoospermia before surgery and in subjects showing oligospermia or azoospermia post surgically were significantly lower (P < 0.05) compared to men with normal sperm count. Serum levels of FSH were significantly elevated (P < 0.05) compared to semen levels in oligospermic men prior to surgery but this increase was not seen in post VEA subjects. These results were discussed.


Effect of prolonged incubation of male rat whole pituitary or pituitary-hypothalamus complex with testosterone on release of gonadotrophin and prolactin in vitro. Investigations were undertaken to study the effect of in vitro addition of testosterone (0.3 mM) on the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL) by pituitary-hypothalamus complex (PHC) or the whole pituitary (PI) incubated for 72 hr, with incubation media changed every 24 hr. PHC or PI were from adult intact or castrated (7 days post castration) rats. The tissues incubated with or without testosterone were further exposed to 0.1 nM luteinizing hormone-releasing hormone (LHRH) for 4 hr. Incubation media and the pituitary were analyzed for PRL and gonadotrophin content. While PHC from normal and castrated rats released increasing amounts of LH with diminishing amounts of FSH and PRL at different periods of incubation, PI showed a decrease in the amounts of gonadotrophin and PRL released. Co-incubation of PHC or PI of intact or castrated rats with testosterone stimulated the release of LH and FSH during the first or second-24 hr incubation but inhibited the release of PRL in all the three incubations of 24 hr each. The extent of PRL inhibition increased with increasing incubation period. Testosterone had no effect on LHRH induced release of PRL but inhibited LHRH induced release of LH and FSH by pituitaries from constructs of normal rats. Testosterone reduced intrapituitary contents of PRL and FSH of intact and castrated rats. The data are interpreted to suggest that hypothalamus is essential for the maintenance of functional pituitary in vitro and that intrinsic differences exist in mechanisms regulating the secretion of LH, FSH and PRL.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunoendocrine interrelationship--effect of ovariectomy on spleen and thymus in mouse. Increase in the weights of spleen were observed 15 days after ovariectomy in adult as well as immature mice. However, no corresponding change was recorded in the splenocyte count. Morphological alterations in the shape of germinal centres was noted after ovariectomy in adult and immature mice. Increase in weight of the thymus could be demonstrated in adult mice only, with a concomitant enlargement of cortical and medullary region.


Role of calcium in secretion of chorionic gonadotropin by first trimester human placenta. The role of calcium in regulation of secretion of human chorionic gonadotropin (hCG) by first trimester human placental minces in vitro has been investigated. Depletion of calcium in the medium by addition of EGTA resulted in a drastic decrease in the levels of immunoreactive hCG in the medium with consequent of accumulation of hCG in the tissue. Addition of A 23187 which is a calcium ionophore resulted in a dose dose dependent increase in the hCG in the medium and this stimulatory response could not be observed in the absence of calcium. Use of lanthanum (a calcium antagonist) in place of calcium in the medium used resulted in a significant decrease in the levels of hCG in the medium. Addition of veratridine (a sodium channel activator) stimulated hCG secretion in a dose dependent manner. These results suggest that calcium is essential for normal secretion of hCG by human placenta.


Duration of antiestrogenecity of compound CDRI-85/287: a new orally active nonsteroidal antiimplantation agent. Duration of antiestrogenic and antiimplantation action of CDRI-85/287, (2-(4-(2-N-piperidino)ethoxy phenyl)-3-phenyl(2H)benzo(2)pyran), was studied in rat. Pretreatment of ovariectomized immature rats with this compound caused translocation of cytoplasmic estrogen receptor (ER) to the nucleus and a marked depletion of cytoplasmic ER pool resulting in a nonresponsive state of the uterus to subsequent estrogen administration until day 4. While in rats pretreated with estradiol, increased cytoplasmic ER level made the uterus responsive to a second injection of estrogen. In the delayed implantation model, 85/287 pretreated rats were given estrone on days 4, 5 or 6 post-antiestrogen treatment. No implantations were observed after estrone administration on day 4, but were present when estrone was given on days 5 or 6. Summation of these results suggests the duration of action of 85/287 to be 3-4 days in rat.


Binding of radiolabelled luteinizing hormone to intact and ovariectomised rat uterus. Binding of ovine LH to uterine tissue preparation from intact and ovariectomised rat clearly indicates that uterus possesses specific binding sites for LH. Binding characteristics of LH to uterine tissue preparation from intact rat showed saturability with high affinity and low capacity. Scatchard plot analysis showed dissociation constant of the specific binding site to be 0.12 x 10(-9) mol/l and the number of binding sites was 2.31 +/- 0.05 f mol/mg protein. Ovariectomy did not change the binding affinity but effected a decrease in the number of binding sites (1.7 +/- 0.08 f mol/mg protein). LH treatment of ovariectomized (ovx) rat had no effect on binding affinity but significantly increased the number of binding sites (3.23 +/- 0.1 f mol/mg protein). Reduction of uterine weight due to ovariectomy and marked increase of ovx rat uterine weight by LH administration indicate a source of estrogen in ovx rat. An in vitro uterine tissue slice (from intact and ovx rat) incubation showed depletion of 17 beta-estradiol (E2) content in ovx rat which significantly elevated on LH addition. Data suggest that LH binding to rat uterine tissue has biological relevance.


Effect of fertility regulating agents on motility and zona-free hamster egg penetration by spermatozoa of bonnet monkey. Administration of STS-557 (17 alpha-cyanomethyl-17 beta-hydroxyestra 4,9(10)-dien-3-one; 12 mg/monkey daily) for 4 weeks either alone or in combination with 20 Aet-1 (testosterone-trans-4-n-butyl cyclohexyl carboxylate; code CDB 1781; 40 mg/monkey single administration) had no significant effect on motility and zona free hamster egg penetration by spermatozoa of bonnet monkey, but continuation of the treatment for 12 weeks reduced (in one monkey treated with STS-557) or abolished (one treated with STS-557 and two with STS-557 + 20 Aet-1) the motility as well as zona-free hamster egg penetration (by spermatozoa of all treated monkeys). Motility and the ability to penetrate zona-free hamster egg returned to normalcy after 10 weeks of withdrawal of treatments. Active immunization of monkeys with ovine FSH (4 weeks after booster) had no adverse effect on motility of spermatozoa but none of the zona-free hamster eggs was fertilized. The correlation between motility and the capacity to penetrate the zona-free hamster eggs by monkey spermatozoa varies with the treatment. Such correlation was apparent in monkeys treated with STS-557 but not in monkeys immunized with ovine FSH.


Ability of deglycosylated human chorionic gonadotropin (dghCG) to block luteal function and establishment of pregnancy in bonnet monkeys (Macaca radiata). The ability of deglycosylated hCG (dghCG) prepared by deglycosylation of a clinical hCG (3000 IU/mg) preparation, to block luteal function during regular cycles as well as luteal rescue in simulated and mated cycles of female bonnet monkeys (M. radiata) has been evaluated. The cycle length (C:28 vs E:24 days) and the total progesterone produced during the luteal phase was significantly reduced (by 45%, P < .05) by injecting 450 micrograms of dghCG/day (in split doses) on days 18, 19, and 20 of cycle. At the doses tested the dghCG used did not exhibit any agonistic activity in the female monkey. In a second experiment injection of 200 micrograms of dghCG/day on days 18-20 of cycle blocked the normal response of the luteal tissue to exogenous hCG (10 micrograms of a 12,000 IU/mg preparation) injected on day 23 of cycle. In a third experiment no pregnancies occurred when a group of 5 animals were injected dghCG (450 micrograms dghCG/day) on days 18-21 of their mated cycle. Animals chosen for this study were proven fertile regularly cycling monkeys and these were cohabited with males between days 9 and 14 of cycle. Each of the monkeys was exposed to 3 consecutive treatment cycles. During post-treatment phase 2 out of 3 monkeys exposed to males became pregnant. The study clearly demonstrates that it is possible to block normal luteal function as well as luteal rescue of the female monkey by using dghCG in the right dose and mode.


Contraceptive potential of an antiprogestin ZK 98.734: reversal of ZK 98.734--induced blockade of folliculogenesis with FSH and LH and their differential effects in bonnet monkeys. Studies were undertaken in adult bonnet monkeys to investigate whether treatment with an antiprogestin ZK 98.734 at weekly intervals, starting from day one of menstrual cycle, could arrest ovulation and also to determine if ZK 98.734 induced blockade of ovulation could be reversed with gonadotropins. Adult animals have ovulatory menstrual cycles of normal duration were treated at weekly intervals with ZK 98.734 (25 mg/dose, sc, oil base) for 10 consecutive weeks and its effects on serum levels of estradiol, bioactive LH and progesterone, and endometrial histology were investigated. Following treatment with the antiprogestin they were treated with hMG or hFSH alone. Ovulation was blocked during treatment period in all the animals (n = 14). Typical follicular phase rise in estradiol levels was inhibited, mid cycle surge in the levels of bioactive LH was abolished and serum progesterone levels remained below 1 ng/ml throughout the treatment period. However, prolonged treatment had no significant effect on the basal levels of estradiol which were around 50 pg/ml. ZK 98.734 also had no significant effect on cortisol levels. In animals (n = 4) followed for recovery after the last dose, the treatment cycle length was increased to 117.8 + 6.8 days. In three animals the treatment cycles were anovulatory, whereas in one delayed ovulation with luteal insufficiency was observed. The endometrium had become atrophic. Treatment with hMG (Pergonal: 35 I.U. hLH and 35 I.U. hFSH) or hFSH (Metrodin, 35 I.U.) for 7 consecutive days initiated folliculogenesis and the animals ovulated either spontaneously or after a single im injection of hCG (100 I.U.) on day 8 in ZK 98.734 treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Manage of acute osteomyelitis in children--should it be conservative? 73 children with acute osteomyelitis seen at King Fahd University Hospital, Al-Khobar, Saudi Arabia were reviewed. Majority of patients were between the 6-10 year age group and male children predominated. All patients had incision and drainage and antibiotic therapy for a minimum of 6 weeks. Metaphysis of the tibia was the commonest site of infection and the staphylococcal species was cultured in 77% of children. Ampiclox was the most sensitive antibiotic. The average follow up was 4.9 years and the incidence of chronic osteomyelitis was 1.75%. In conclusion this study confirms that clinically it is not possible to detect a subperiosteal abscess within the first 48 hours. As blood culture is not 100% reliable in isolating the ineffective organism and incision and drainage plays a double role, firstly in the identification of the offending organism and secondly in the evacuation of pus. A six-week antibiotic therapy is essential to prevent any relapses. The correct management of acute osteomyelitis in children is surgical drainage of the affected site combined with antibiotic therapy.


Serum electrolytes and osmolality in diabetes mellitus. Fasting plasma glucose levels, serum osmolality and serum concentrations of sodium and potassium were determined in 73 Libyan diabetic patients attending the outpatient clinic of the Diabetes Hospital, Tripoli, Libya. The respective mean values were 234.8 +/- 9.7 mg.dl-1, 288.5 +/- 2 m0sm.L-1, 134.7 +/- 0.8 mEq.L-1 and 4.2 +/- 0.07 mEq.L-1. Statistically significant correlations were present between fasting plasma glucose and serum osmolality as well as the concentrations of serum sodium and potassium. There is is an increase in osmolality and levels of sodium and potassium concentration with an increase in plasma glucose concentration.


High dose aerosol pentamidine for secondary Pneumocystis carinii pneumonia prophylaxis in AIDS patients. In a prospective trial of aerosolized pentamidine as secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) 18 patients received 400 mg once weekly for a mean period of 15.5 months. Pentamidine aerosol was administered with an MA2 jet nebulizer. No PCP relapses were observed and no serious side effects occurred.


Cerebrospinal fluid neopterin and beta 2-microglobulin levels in neurologically asymptomatic HIV-infected patients before and after initiation of zidovudine treatment. The effect of zidovudine on beta 2-microglobulin and neopterin in the cerebrospinal fluid (CSF) was studied in ten HIV-seropositive neurologically healthy individuals. CSF concentrations of neopterin decreased by 53% (from 20.3 to 9.5 nmol/l, p < 0.01) and beta 2-microglobulin by 36% (from 2.8 to 1.8 mg/l, p < 0.01) four to eight months after initiation of therapy.


Transintestinal elimination of ciprofloxacin in humans--concomitant assessment of its metabolites in serum, ileum and colon. Ciprofloxacin (200 mg) was infused to seven patients at the beginning of elective colorectal surgery. Thirty minutes after the end of infusion (i.e. 60 min after the start of the operation) ciprofloxacin reached concentrations of 1.60 mg/l in serum and of 3.42-6.07 mg/kg fresh weight in the ileum and colon. During the next 30 min (90 min after the start of operation) the concentration of ciprofloxacin in serum decreased to 86% of its initial level, but this decrease was less rapid than that observed in the ileal (to 56.8%) or colonic (to 74.8%) mucosa. Three metabolites could be identified (desethylen-, sulpho-, oxociprofloxacin). Initially, at 60 min the amount of these metabolites was about 15% of the total drug concentration in serum, but only 2-3% of that in the gut tissues. At 90 min the relative amount of metabolites was increased in serum as well as in the gut tissues. It is concluded that transintestinal elimination of ciprofloxacin is a general feature of the whole gut. Obviously, the elimination process is not due to degradation of ciprofloxacin within the gut wall.


Risk factors of HIV-1 infection among female prostitutes in Khon Kaen, Northeast Thailand. HIV infection has increased to epidemic proportions in Thailand since 1987. There have been separate epidemics among population groups at high risk of infection and significant increases in different localities. The northeast region of Thailand has been affected by the epidemic since early 1989. The purpose of this study was to identify factors associated with HIV transmission among prostitutes during an early phase of the epidemic in the regional center of Khon Kaen. Three hundred and fifty-six prostitutes known to work in the urban area of Khon Kaen (Ampur Muang) in November 1990 were included in the study. Prostitutes were divided into two groups according to the type of place where they worked: direct prostitutes (in brothels, n = 217) and indirect prostitutes (in massage parlors, n = 139). The prevalence of HIV infection was found to be 12% among direct prostitutes and 2% among indirect prostitutes. Four variables were significantly associated with HIV infection after adjusting for confounders by logistic regression analysis: previous work in an area of high HIV prevalence, working in Khon Kaen less than one month, a low price charged for sex and using injectable contraceptives. Follow-up investigations are currently being carried out to explore in detail the association between the use of injectable contraceptives and HIV infection.


Carriage of methicillin-resistant Staphylococcus aureus by non-hospitalized subjects in Israel. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the anterior nares and axilla was studied in 920 non-hospitalized subjects: 350 drug addicts, 350 individuals presenting at a hospital emergency room for various reasons, and 220 hospital health care workers. S. aureus was isolated from 105 (11.4%) subjects, in six (6.3%) of whom the isolates were methicillin-resistant. The isolation rate of the organism and the prevalence of resistant strains in the different subgroups were, respectively: drug-addicts, n = 32 (9.1%), n = 2 (6.9%); emergency room patients, n = 36 (10.2%), n = 1 (3.2%); and hospital health care workers, n = 37 (16.8%), n = 3 (8.5%). Our findings suggest that MRSA remains uncommon in the community, while the prevalence of S. aureus carriage (including methicillin-resistant strains) in hospital personnel is quite similar in divergent geographical areas.


Hepatosplenic candidiasis, a fatal disease? We report on two patients with acute leukemia and prolonged granulocytopenia after cytotoxic therapy in whom the diagnosis hepatosplenic candidiasis was made. Both patients developed upper abdominal discomfort with elevated alkaline phosphatase after resolution of granulocytopenia. The diagnosis was established by demonstration of multiple abscesses in liver and spleen on ultrasound and computed tomography. Both patients were initially treated with amphotericin B i.v., one of them received liposomal amphotericin B (cumulative dose of 2,530 mg and 570 mg, respectively). Thereafter, therapy was continued for months with oral fluconazole. The treatment of hepatosplenic candidiasis was successful, however, the patients died from relapse and progression of leukemia.


Resistance of recent Neisseria gonorrhoeae isolates in Nigeria and outcome of single-dose treatment with ciprofloxacin. One hundred four patients (71 males, 33 females) with acute gonococcal urethritis or cervicitis were treated with a single oral 250 mg dose of ciprofloxacin at Jos University Teaching Hospital, Jos, Nigeria. All gonococcal strains were isolated from appropriate pre-treatment swabs. Penicillinase-producing Neisseria gonorrhoeae (PPNG) accounted for 72.8% of all isolates. In vitro sensitivity of gonococcal isolates to ciprofloxacin was 100%, while that to penicillin, ampicillin and co-trimoxazole was below 15%. Of the 104 patients treated with ciprofloxacin, 73 (70%) attended a follow-up visit. Seventy-three (100%) patients showed clinical cure and elimination of N. gonorrhoeae from the respective site of infection. Post-gonococcal urethritis or cervicitis believed to be due to concomitant chlamydial infection was found in 22 (30.1%) patients--18 males and four females. No adverse reactions were reported by any patient. Our findings show that a single oral dose of ciprofloxacin (250 mg) is well tolerated and effective in the treatment of uncomplicated gonorrhoea and is particularly useful in regions with a high prevalence of PPNG.


Active immunization with pC protein of Borrelia burgdorferi protects gerbils against B. burgdorferi infection. Serious infection due to Borrelia burgdorferi and the disseminated infection characteristic of the disease possess unique treatment problems. The wide and still increasing incidence of Lyme borreliosis as well as the problems in treatment call for effective prevention strategies by active immunization. Vaccination experiments were done to determine if active immunization of gerbils with recombinant OspA and pC protects against infection with strains of B. burgdorferi. Gerbils were vaccinated with recombinant OspA and pC (20 kDa protein) and challenged four weeks later with a clone (derived from B. burgdorferi strain PKo) which expresses an abundant amount of pC but only little OspA. Non-immunized gerbils challenged with the same B. burgdorferi strain were used as controls. Both groups of immunized gerbils developed antibodies against the recombinant vaccines. The pC vaccinated group was protected against infection, whereas the OspA vaccinated group showed signs of infection. The non-vaccinated group developed generalised infection. These results show that pC should be considered as a further vaccine candidate and probably needs to be combined with OspA for an efficient vaccine against B. burgdorferi.


Intracellular bactericidal activity of fosfomycin against staphylococci: a comparison with other antibiotics. The intracellular bactericidal activity of fosfomycin was compared to that of other anti-staphylococcal agents. Two staphylococcal strains (one isolate of Staphylococcus aureus and one isolate of Staphylococcus epidermidis) were incubated in vitro with human granulocytes isolated from volunteers. After phagocytosis and removal of residual extracellular bacteria, the cells were resuspended in the presence of clinically relevant concentrations of fosfomycin, teicoplanin, vancomycin and rifampin. The number of bacteria surviving intracellularly was determined by colony counts after osmotic lysis of the granulocytes at different time intervals. Incubation with fosfomycin resulted in a mean reduction of intracellular bacteria by approximately two logs of ten within 18 h for both staphylococcal strains. Although less effective than rifampin, fosfomycin showed a significantly higher intracellular activity than the glycopeptide antibiotics in this model.


The non-enzymatic inactivation of thirteen beta-lactam antibiotics in human faeces. In order to obtain a method that could predict the in vitro inactivation of an antibiotic in the digestive tract, the non-enzymatic inactivation of 13 beta-lactam antibiotics by human faeces was investigated. Benzylpenicillin, amoxicillin, amoxicillin/clavulanate, cloxacillin, piperacillin, temocillin, cefuroxime, cefamandole, cephradine, cefotaxime, ceftazidime, aztreonam and imipenem were mixed in six graded concentrations with faecal suspensions of 30 healthy volunteers. After incubation the remaining antimicrobial activity was measured by means of a serial dilution method. A relationship between the initial antibiotic concentration (Aia) and the remaining antimicrobial activity after incubation (Asd) was derived, namely: Asd = 1/2[(Aia-K-F)+square root ((Aia-K-F)2 + 4 K Aia)]. The parameters K and F represent the intrinsic dissociation constant and the amount of available bindingsites in the faeces, respectively. Asd values were predicted with a reasonable degree of accuracy for all thirteen antibiotics. Dissociation constants differed significantly between the penicillins and the cephalosporins but F- values did not differ between cephalosporins and penicillins.


The effect of liposomal cefoperazone against Pseudomonas aeruginosa in a granulocytopenic mouse model of acute lung infection. The therapeutic efficacy of liposomal cefoperazone against Pseudomonas aeruginosa was investigated in a granulocytopenic mouse model of acute lung infection. Granulocytopenia was induced in mice by intraperitoneal (i.p.) injection of 200 mg/kg cyclophosphamide. Mice were challenged by exposure to an aerosol containing P. aeruginosa and were treated i.p. with liposomal cefoperazone prepared by the dehydration-rehydration method. The half-life of free cefoperazone in the lungs following i.p. administration of the liposomal drug was significantly lengthened (13 min vs. 261 min), and the cefoperazone activity in the lungs remained above the MIC longer after administration of liposomal cefoperazone than after treatment with cefoperazone. Liposomal cefoperazone was more effective than cefoperazone alone in preventing death of granulocytopenic mice from lethal pulmonary challenge with P. aeruginosa (75% vs. 38% survival, p = 0.031). Finally, P. aeruginosa was cleared faster from the lungs of mice treated with liposomal cefoperazone when compared with those treated with cefoperazone. This study shows that incorporation of cefoperazone into liposomes enhances the activity of the antibiotic against P. aeruginosa in a granulocytopenic host.


Successful treatment of brain abscess caused by Nocardia in an immunocompromised patient after failure of co-trimoxazole. Disseminated infection caused by Nocardia asteroides is a fairly rare entity occurring mostly in immunocompromised states. Metastatic brain abscesses are a frequent and ominous complication. We report on a patient whose underlying disease was stage II pulmonary sarcoidosis. He acquired disseminated N. asteroides infection while on immunosuppressive therapy with prednisolone. After the generally recommended therapy with co-trimoxazole (trimethoprim/sulfamethoxazole) proved ineffective in controlling his brain abscesses, the lesions of the central nervous system completely resolved under a combination of oral rifampicin with i.v. imipenem, followed by oral rifampicin and ampicillin/clavulanic acid.