Testicular descent: new insights into its hormonal control.
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Biomedical subjects
Publications and source records attributed to J M Hutson.
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The effect of vibroacoustic stimulation on the nonstress test at gestational ages of less than or equal to 32 weeks was studied in 15 patients who underwent a total of 316 nonstress tests starting at 20 to 25 weeks' gestation. There were 168 nonreactive nonstress tests that were followed by 3 seconds of vibroacoustic stimulation. The incidence of reactive nonstress tests after vibroacoustic stimulation was significantly increased after 26 weeks' gestation. This may have clinical applicability and may be related to functional maturation of the fetal auditory system.
This study examined the reported association between cerebral palsy and cryptorchidism. A comparison was made among 25 boys with cerebral palsy under the age of 2 years and 6 months, 25 boys with cerebral palsy aged between 5 and 10 years, and age-matched controls. The testes remained in the same position with age in boys with cerebral palsy, whereas in normal children the testes were slightly lower initially (P less than .005) and became lower still with growth (P less than .001). This result, taken in conjunction with previous studies, casts doubts on the theories of early damage to the hypothalamic-pituitary-gonadal axis as the cause of maldescent in cerebral palsy. It is postulated that any apparent increase in cryptorchidism in older patients with cerebral palsy may be caused by spasticity of the cremaster muscle leading to pathologic retraction of the testis out of the scrotum.
Forty-three patients with abruptio placentae before 35 weeks of pregnancy were managed expectantly with observation or with tocolytic therapy when contractions were present. Mean time to delivery was 12.4 days. Twenty-three patients were delivered within 1 week of admission. In the remaining 20 patients, the mean time to delivery was 26.8 days. There were no intrauterine deaths. In properly selected patients with preterm gestation and low-grade abruptio it is reasonable to defer delivery. These patients must be followed closely with antepartum fetal heart rate monitoring, serial hematologic and coagulation profiles, and serial sonograms when indicated.
The purpose of the present study was to quantify beta cell proliferation in rabbits that had undergone subtotal beta cell ablation by labeling cell nuclei undergoing DNA synthesis with bromodeoxyuridine (BUdR). Ten New Zealand white rabbits were compared with five sham-operated controls. The beta cells in the head of the pancreas were destroyed by intravenous alloxan (200 mg/kg) while the tail of the pancreas was temporarily isolated from the systemic circulation by vascular occlusion clamps. On day 7, BUdR (70 mg/kg) was infused prior to killing to label newly synthesised DNA. Immunoperoxidase staining with anti-insulin sera and an anti-islet cell monoclonal antibody confirmed the absence of insulin-producing cells in the head of the pancreas. Beta cell proliferation within the islets of the tail of the pancreas was suggested by the appearance of cells undergoing mitosis and confirmed by BUdR labeling of cell nuclei detected with anti-BUdR monoclonal antibody. The mitotic index was significantly increased compared to control rabbits (p = 0.0235, Mann-Whitney U nonparametric test). This study demonstrates that the BUdR labeling can be used to document beta cell proliferation in vivo in the rabbit model after subtotal beta cell ablation.
The maternal morbidity associated with the type of uterine incision used for the delivery of the very low birthweight (VLBW) fetus was examined. Maternal morbidity factors evaluated included the incidence of infection, bleeding, wound complications, estimated blood loss, blood transfusions, fever and days in hospital. Cesarean section was performed in 115 of 197 VLBW infants, with 31 low transverse and 84 vertical cesarean sections. There were no significant differences in antepartum, intrapartum or postpartum data between these two groups. Short term maternal morbidity was not increased with the use of vertical compared with low transverse cesarean section for the delivery of the VLBW fetus.
A study was conducted to determine the safety and utility of autologous blood donation in third trimester pregnancy. Thirty-seven obstetric patients, 32 with an obstetric risk factor, donated an average of 485 ml of blood. Twenty-one of the 37 patients were expected to undergo cesarean section. Nonstress testing was performed before and after phlebotomy. Continuous fetal heart rate monitoring was maintained throughout the donation, which lasted an average of 9 minutes. All nonstress test results were normal before and after the phlebotomy except in one case. All fetal heart rates remained stable during phlebotomy and premature labor was not precipitated. All fetal outcomes were normal. One patient delivered on the day of phlebotomy, 6 hours after the procedure. Only one of the autologous units was used, in a patient who had a pelvic infection and moderate anemia. The incidence of primary cesarean section was 35%. Phlebotomy of the mother appears to be safe for the fetus at term. Further investigation is needed to determine the safety of removal of more than 1 unit of blood and blood donation at earlier gestational ages.
Most congenital lateral cervical cysts, fistulae, and skin tags are considered to be from the branchial apparatus. This is a 13-year review of 58 patients (with 66 branchial lesions) who were operated on. There were eight simple cysts and six cysts with a fistula; 43 external fistulae with or without an internal opening, and nine skin tags. Eighty-seven percent (39/45) of patients with skin tags and external fistulae were less than 5 years of age at the time of operation. On the other hand, all eight patients with cysts but no fistula were greater than 9 years of age. Eight lesions were considered to be the first branchial remnants, and 44 lesions were suspected to be from the second branchial cleft. One external fistula with an internal communication to the pharynx at the level of thyrohyoid membrane was considered to be a third (or fourth) branchial remnant. The other branchial cyst with thyroid tissue in its wall was suggested to be a fourth branchial remnant. Pathology of the excised lesions showed columnar, squamous, or a mixed epithelium. Lymphoid aggregates were documented in 31 patients. Duration of hospital stay was short, except for four patients with first cleft defects who stayed more than five days. Three of the four recurrent cases were first branchial remnants, including one case with the first operation performed at another hospital. In view of these findings, first branchial remnants must be excised with extra care.
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In spina bifida there is a high incidence of cryptorchidism, particularly where the lesion is at or above L2. This article describes the location of the testis in 32 spina bifida patients and the effect of spinal cord transection in neonatal rats: both studies suggest that the spinal cord influences testicular descent. It is already established that androgens, an intact genitofemoral nerve, and the gubernaculum are essential for the transinguinal phase of testicular descent to occur. Yet the mechanism by which testosterone exerts its effect on the gubernaculum remains obscure. To account for all the observed phenomena we postulate that a spinal cord nucleus may exist that is sensitive to androgens and mediates impulses through the genitofemoral nerve to the gubernaculum. Neuronal modulation of the gubernaculum may induce testicular descent.
The proximal and distal attachments of the gubernaculum were severed in neonatal rats to examine their role in testicular descent and their relationship to transection of the genitofemoral nerve, which prevents descent of the testis. In 34 of 82 animals proximal transection of the gubernaculum resulted in descent of the testis. In 18 animals the testis remained in the abdomen but in both groups the processus vaginalis developed, suggesting that failure of descent was accidental and not caused by scrotal maldevelopment. Distal transection resulted in failure of descent and prevented growth of the processus vaginalis in all 27 rats. These results suggest that distal transection of the gubernaculum is equivalent to division of the genitofemoral nerve, which supplies the gubernaculum through its distal attachment. Because denervation of the gubernaculum prevents the effect of androgens on gubernacular differentiation, the results suggest that testosterone acts via the nerve. The putative effect of androgens on the gubernaculum may be mediated indirectly by the central nervous system, rather than directly on the gubernaculum itself.
The utility of antepartum fetal heart rate (APFHR) monitoring (nonstress test and the contraction stress test) was evaluated for a 10-year interval from 1974 through 1983. The number of high-risk patients evaluated increased from 2.9 to 25.1% of all deliveries. The decade's perinatal mortality rate differed from 22.4 per 1000 in the nontested population to 11.8 per 1000 in the tested population; the stillbirth rate differed from 11.1 per 1000 to 5.4 per 1000 uncorrected, 2.2 per 1000 corrected, and perinatal morbidity also differed from 26.1 per 1000 to 24.9 per 1000 (NS). Improvement statistics appear to plateau by the fourth year. An abnormal APFHR test was associated with a lethal congenital anomaly in 2.54% of patients (versus 0.5 to 1.5% in the general population). Evaluation for the presence of congenital anomalies appears to be indicated in the fetus with an abnormal APFHR test. A lower stillbirth rate occurred within 4 days of a normal APFHR test (0.027%) compared with a test interval of 5 to 7 days (0.11%). Thus, APFHR testing performed twice weekly may offer a better outcome for the fetus at risk than once weekly testing. This report confirms that the chief value of APFHR testing is its ability to identify the normal healthy fetus. These tests are somewhat less accurate at identification of the sick fetus. The nonstress test and contraction stress test were found to be of similar clinical predictive value.
Six girls with the non-salt-losing form of congenital adrenal hyperplasia are described. Diagnosis was delayed in five, the range of ages of diagnosis being 19 months-7 years. In the sixth, despite early diagnosis and medical treatment, surgery was delayed electively until she was 3 years old. The five in whom diagnosis was delayed were all virilized with a markedly advanced bone age and reduced adult height prognosis. Diagnosis was delayed for a variety of reasons: misinterpretation of laboratory data (one), lack of availability of medical assistance (one), language problems (one), maternal inexperience (one), and failure of the doctor to recognize an obvious clinical abnormality (one). All six children came from immigrant families, and all except one was born in a major centre. None was born before 1979.
Diethylstilbestrol (DES) feminizes chick embryos in ovo, preventing regression of the Mullerian ducts (MDs). The feminized testis, however, despite its ovarian-like appearance, continues to produce Mullerian inhibiting substance (MIS). This study was designed to test whether exogenous DES preserved the MD against endogenous MIS by affecting the target organ (feminization). DES (0.1 mg) was injected into the air sacs of 5-day-old chick embryos. Testes were obtained from 15-day-old chick embryos and MDs from 8-day-old chick embryos and combined in organ culture for 72 h. MD regression was examined macroscopically and microscopically after 3 days in vitro in medium without DES (group A: n = 155) and with 10(-6) M DES (group B: n = 169). Four types of coculture were set up as follows: 1) Control testis with control MD; 2) DES-treated testis with DES-treated MD; 3) Control testis with DES-treated MD; 4) DES-treated testis with control MD. In medium without DES (group A), MD regression was inhibited significantly when the duct was pretreated with DES [2) and 3) vs. 1) and 4)]. The pretreated testis produced slightly less regression [4) vs. 1)], but this was not significant. Previous studies in ovo had suggested that estrogen prevented MD regression directly as well as causing feminization of the testis, because MIS secretion was not inhibited from the feminized gonad. These results show that pretreatment of the MD with DES blocks regression in vitro by a normal testis, confirming that the primary site of action of estrogen is on the duct itself.
The ontogeny of Müllerian inhibiting substance (MIS) production by the developing testis of an Australian marsupial, the tammar wallaby (Macropus eugenii), was determined during pouch life using an organ-culture bioassay of mouse fetal urogenital ridge. This information was related to the morphological events during testicular migration and descent. MIS biological activity was found in testes (but not ovaries or liver) of pouch young from 2 to 85 days of age. MIS production had commenced by day 2, which is within a day of the first gross morphological signs of testicular differentiation. Müllerian duct regression occurred between 10 and 30 days, which partly coincided with testicular migration to the inguinal region and enlargement of the gubernacular bulb (15 to 30 days). These observations are consistent with the hypothesis that MIS may be involved in testicular transabdominal migration. The epididymis commenced development and growth only after the testis had descended through the inguinal ring. This provides no support for the suggestion that the epididymis is involved in testicular descent into the scrotum. The basic sequence of events in post-testicular sexual differentiation in the wallaby is sufficiently similar to that seen in eutherian mammals to make it an excellent experimental model for future studies of testicular differentiation, migration and descent.
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Antepartum fetal monitoring was initiated at 19 to 26 weeks' gestation in 15 pregnancies: six (five with systemic lupus erythematosus, one with circulating anticoagulant) with a complicated antepartum course (group 1); three, all systemic lupus erythematosus, with a normal antepartum course (group 2); and six normal control pregnancies (group 3). Group 1 all exhibited nonperiodic fetal heart rate decelerations, without the classical appearance of early, late, or variable decelerations, and four of the six had fetal bradycardia. In three group 1 cases, there was no active intervention because of early gestational age, and fetal death occurred at 23, 27, and 27 weeks, respectively. The other three patients in group 1 received betamethasone and were delivered by cesarean section at 28 to 30 weeks. There were no cases of respiratory distress syndrome or neonatal death. Five of the six infants in group 1 were small for gestational age. The nonperiodic fetal heart rate decelerations were absent in both groups 2 and 3 who all had normal fetal outcomes at term. The abnormal finding of women with nonperiodic fetal heart rate decelerations at 20 to 28 weeks may detect the fetus at risk for intrauterine death in pregnancies complicated by systemic lupus erythematosus or circulating anticoagulant. Continued surveillance, steroid induction of lung maturity, and delivery should be considered in these cases.