Monosodium glutamate admlinistration to the newborn reduces reproductive ability in female and male mice.

Monosodium glutamate (MSG) administered during the neonatal period (days 2 to 11) resulted in a sequence of events that were manifested in adulthood. Reproductive dysfunction was seen in both female and male animals. Females treated with MSG had fewer pregnancies and smaller litters, while males treated with MSG showed reduced fertility. The MSG-treated mice showed increased body weight and decreased pituitary, thyroid, ovary, or testis weights.

Receptive field properties of simple and complex striate neurons in Siamese cats.

Responses of striate cortical cells in Midwestern Siamese cats to moving slits and stationary flashed spots were recorded and compared to similar data in common cat controls obtained under identical experimental conditions. Over 90% of the neurons sampled had receptive fields within 10 degrees of the area centralis. The proportion of binocularly excited cells in Siamese striate cortex was less than that found in the control cats, but more than has previously been reported, and was inversely related to the extent of convergent misalignment exhibited by each animal. Those striate neurons which could be driven by either eye had normal binocular receptive fields and demonstrated normal binocular interaction effects except facilitation. Receptive field dimensions (length, width, area) were significantly larger in Siamese than in common cats. For the simple cells, strabismic Siamese cats had larger receptive fields than orthophoric Siamese cats. Average spontaneous activity in Siamese cats was significantly higher than in the controls. However, similar encounter rates of simple, complex, and hypercomplex units were observed in both Siamese and common cats, and peak responses were not different. Velocity preference in complex Siamese units was shifted to slower velocities compared to common cat complex cells. A loss of direction selectivity was also revealed in the Siamese simple and complex neurons. Finally, sharpness of orientation tuning was dramatically reduced in Siamese complex cells, and this reduction was directly related to the extent of convergent squint exhibited by each animal. The results are discussed in terms of developmental anomalies and neurophysiological retinal abnormalities in Siamese cats.

Double-blind, placebo-controlled crossover study of folinic acid (Leucovorin for the treatment of fragile X syndrome.

We conducted a randomized, double-blind, placebo-controlled crossover study of folinic acid therapy (dl-Leucovorin, 15 mg/day) or placebo for males with Fragile X (fra(x)) syndrome. Twenty-one patients were enrolled in the study. The treatment periods were 3 months in length. Patients were followed with chemistry panels and complete blood counts. No differences between placebo and treatment phases were noted in any laboratory parameter. Instruments to measure functioning were the Vineland Adaptive Behavioral Scales, Peabody Picture Vocabulary Test-Revised, Conners Parent and Teaching Rating Scales, the ADD-H: Comprehensive Teacher's Rating Scales (ACTeRS), and a questionnaire designed by the investigators. At the crossover point, 2 parents requested to withdraw from the study because they felt their children had made dramatic gains during the first half of the study and had lost those gains after the crossover point. Both parents had accurately predicted that their sons were receiving folinic acid during the first half of the study. However, no statistically significant differences could be demonstrated between the treatment and placebo phases of the study with any instrument when the results were averaged over the entire cohort. After the conclusion of the study, approximately one-half of the parents believed that their children had benefitted from the folinic acid therapy and elected to continue treatment. Thus far, no significant side effects have been noted from long-term folinic acid therapy so we are offering all Fragile X patients a 3-month trial of medication.

Body smuggling of illicit drugs: two cases requiring surgical intervention.

The smuggling of illicit drugs by concealing them within the human body has become a widespread practice. Those individuals who transport packaged drugs are commonly known as "body packers" or "mules". "Body stuffers," on the other hand, are individuals who emergently place the contraband in a body orifice when they sense apprehension is imminent. In the latter instance, the drugs are not well packaged for transportation by human "consumption," hence the high risk for leakage. These individuals require prompt surgical attention under two circumstances: when they are found to suffer from drug overdosage caused by inadvertent leakage or when obstruction in the body is caused by the drug-laden bags. Two such cases are reported. The first patient presented with acute drug overdose and required an emergency laparotomy. The second patient presented with pyloric obstruction and was treated by endoscopic removal of the bag. One must be aware that these patients are walking time bombs, carrying drugs that may be well packed but have the potential to deliver a lethal dose without warning. Knowledge of the type of drug and type of packaging are essential in managing these patients. The overall plan should be close observation, careful monitoring, conservative therapy, and expectant rapid surgical intervention as needed.

Small-bowel obstruction by an inflatable penile prosthesis reservoir.

Early experience with the inflatable penile prosthesis has been plagued with high failure rates. With improvements in design and surgical technique, the relative incidence of mechanical failures has decreased from 69.9% of all complications to 38.2%, increasing the relative importance of pathologic failures (from 27.3% to 56.4%). The overall complication rate has decreased from an initial 32.5% to 9.0% in recent series. A unique case of small-bowel obstruction caused by intraluminal migration of the reservoir of an inflatable penile prosthesis is described. It was successfully managed by resection of the affected bowel loop and extraperitoneal reimplantation of the reservoir. Although general surgeons are not involved in the placement of these devices, it is important for us to be aware of the possibility of erosion and migration of the component parts, which may result in potentially lethal gastrointestinal and other complications that we may be called on to assess.

Adult foregut duplication.

We report a gastric duplication in a 23-year-old man. The case is unique because the stomach is the rarest location for enteric duplication, the duplication almost never occurs in adults, and the duplication consisted exclusively of pancreatic tissue. This extreme example illustrates the close embryologic and anatomic association between stomach and pancreas. A case is made for the use of the general term of foregut duplication to avoid confusing nomenclature.

Management of penetrating juxtahepatic inferior vena cava injuries under total vascular occlusion.

BACKGROUND: Juxtahepatic inferior vena cava injuries are often lethal. Various operative strategies have been used to improve outcome, but the mortality rate reported in the literature is 80 percent or more. The atriocaval shunt has been advocated for isolation of bleeding retrohepatic vena cava, but recent reports suggest that mortality might be even higher in patients selected for shunting, perhaps owing to ongoing hemorrhage because of indecision and delay prior to insertion, or to technical difficulty with insertion. A series of patients with juxtahepatic inferior vena cava injuries treated successfully with total vascular isolation and occlusion were studied. STUDY DESIGN: Consecutive series of 10 patients with penetrating injuries to the juxtahepatic inferior vena cava were treated at an urban, university-affiliated Level I trauma center. A rapid and direct approach was used along with isolation techniques similar to those used in liver transplantation and elective resection for neoplasm. As resuscitation continued, repair of the inferior vena cava was accomplished in a bloodless field, created by manual compression of the liver, wide exposure, portal inflow occlusion, and proximal and distal control of the inferior vena cava. Aggressive fluid resuscitation and transient aortic cross-clamping controlled resulting systemic hypotension. RESULTS: Mean injury severity score was 26 and mean penetrating abdominal trauma index score was 28. After exposure, three patients had tangential injuries controlled by undersewing a partially occluding clamp. Subdiaphragmatic aortic cross-clamping was performed if total occlusion of the inferior vena cava reduced systolic blood pressure to 60 mm Hg, which was necessary in the remaining seven patients. Nine patients survived surgery, and seven of nine survived to hospital discharge. One postoperative death was a result of multiple organ dysfunction syndrome, and the other of necrotizing bacterial pneumonia. CONCLUSIONS: Total vascular occlusion with selective use of aortic cross-clamping yielded 70 percent survival in an injury that historically has been associated with survival of 20 percent or less. Minimization of visceral ischemia is accomplished by occluding the aorta only after complete isolation of the inferior vena cava.

Inflammatory breast carcinoma: a community hospital experience.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare form of rapidly progressive breast cancer. We reviewed the diagnosis, treatment, and outcome of IBC in our inner city community-based hospital and compared results with previous published reports. STUDY DESIGN: Twenty-five patients were diagnosed and treated for IBC at the Catholic Medical Center of Brooklyn and Queens during the 6-year period of January 1989 through December 1995. Criteria for inclusion in this study were clinical or histopathologic evidence, or both, of inflammatory carcinoma. RESULTS: IBC comprised 2.0% (25 of 1,257) of all breast cancer patients initially diagnosed during this study. All presented with clinical signs of IBC. Invasion of dermal lymphatics by neoplastic cells was demonstrated in 68% (17 of 25) of biopsy specimens. Sixty-eight percent (17 of 25) of patients presented with metastatic (ie, stage IV) disease and 28% (7 of 25) with stage IIIb; one patient (4%) died before staging. Estrogen and progesterone receptor studies were done on 72% (18 of 25) of all specimens. Of those patients who died, 85% were estrogen and progesterone receptor negative; of those surviving, 60% were estrogen receptor positive. Twenty (80%) of the 25 patients died, after a mean survival of 11.8 months and 5 (20%) remain alive, with a mean survival of 44.8 months. Of those who died, 85% were stage IV at presentation. All five survivors were stage IIIb at presentation. Patients underwent a variety of multimodal therapies. Survival was significantly associated with earlier stage at diagnosis and estrogen receptor positivity. CONCLUSIONS: IBC is characterized by rapid progression and dismal outcome. Earlier stage at diagnosis and positive estrogen receptor status suggest a more favorable prognosis. Neoadjuvant chemotherapy, as part of a multimodal approach, has significantly improved the outcome for IBC, but this is limited to patients with stage IIIb disease. Most of our patients presented with stage IV disease. If improvement is to be realized at the community level, limited health care resources must be directed toward aggressive physician and public education.

Behavioral evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine.

Clonidine (CLON), is a widely used antihypertensive agent with a potential for expanded therapeutic application in combating drug withdrawal symptoms in opiate and alcohol addiction. Recently, CLON and an analogue lofexidine (LOF) have been shown to block the opiate withdrawal syndrome in a variety of species, including man. One new application of these agents may be as an alternative to methadone maintenance for pregnant opiate addicts. Any consideration along these lines will require screening for reproductive outcome and behavioral teratogenic effects. Dams were given s.c. injections of CLON (0.16 or 0.64 mg/kg) of LOF (0.64 or 2.56 mg/kg) once daily from gestational day (GD) 8-20. Neonatal body weights, at postnatal days (PNDs) 2, 15 and 30 were reduced in a dose-dependent manner, with LOF-induced reduction twice that of CLON. No significant differences were obtained on negative geotaxis, an auditory startle test, or a series of swimming immobilization tests across the periadolescent period. A series of activity measures carried out on PND 12, 14, 16 and 18 showed minor differences in the high dose LOF male animals, but not in any of the other drug-treated groups.

Neurochemical evaluation of rats prenatally exposed to the adrenergic agonists clonidine and lofexidine.

Clonidine (CLON), an alpha-2 adrenergic agonist, is widely used to reduce hypertension; it is also recommended for blocking acute opiate withdrawal. Lofexidine (LOF), a CLON analog, is an investigational compound being readied for the marketplace. Since exposure to both drugs is likely to occur in the last two trimesters of human pregnancy, it is important to determine whether such exposure can have effects upon brain or behavior of offspring. Pregnant CD rat dams were given daily subcutaneous injections of saline, CLON, or LOF on days 8 through 20 of gestation. Maternal weight during gestation, neonatal weight and neurochemical measures were monitored. Maternal body weight was reduced in a dose dependent manner. At PND 1 brain ornithine decarboxylase (ODC) activity was reduced in LOF- but not CLON-exposed pups of both sexes. At this age no alteration was seen in whole brain catecholamine levels or in whole brain alpha-2-adrenergic binding.

Perforated colorectal carcinomas.

BACKGROUND: Colorectal carcinomas that present with perforation are stated in the literature to carry a poor prognosis. This study is to verify or refute the dismal connotation associated with perforated colorectal carcinomas (PCCs). METHODS: A retrospective analysis of 1551 patients with colorectal carcinoma revealed that 51 (3.3%) patients presented with perforation. Mary Immaculate and St. John's Queens Hospital Divisions of the Catholic Medical Center of Brooklyn and Queens chart and tumor board data were retrieved for the period 1983 through 1993. RESULTS: Localized perforation with abscess formation occurred in 31 (61%) patients, and free perforation with generalized peritonitis in occurred 20 (39%) patients. Sixteen (31%) patients had distant metastasis at diagnosis with a mean survival of only 6 months. Overall operative mortality rate was 12%, and overall 5-year survival rate was 32%. By excluding 16 patients with documented Stage IV disease at diagnosis and 6 operative mortalities (3 of whom also had Stage IV disease at diagnosis), the remaining 32 patients had a mean survival of 59 months and a 5-year survival of 58%. CONCLUSION: In view of the 58% survival in our subset of patients, aggressive management is recommended. This includes management of sepsis and radical surgical resection of adjacent involved organs. A negative attitude associated with PCC is not substantiated in this retrospective 10-year study.

The duration of antibiotic administration in penetrating abdominal trauma.

BACKGROUND: The epidemiology of penetrating abdominal trauma is changing to reflect an increasing incidence of multiple injuries. Not only do multiple injuries increase the risk of infection, a very high risk of serious infection is conferred by immunosuppression from hemorrhage and transfusion and the high likelihood of intestinal injury, especially to the colon. Optimal timing and choice of presumptive antibiotic therapy has been established for penetrating trauma, but duration has not been studied extensively in such seriously injured patients. The purpose of this study was to test the hypothesis that 24 hours of antibiotic therapy remains sufficient to reduce the incidence of infection in penetrating abdominal trauma. METHODS: Three hundred fourteen consecutive patients with penetrating abdominal trauma were prospectively randomized into two groups: Group I received 24 hours of intravenous cefoxitin (1 g q6h) and group II received 5 days of intravenous cefoxitin. The development of a deep surgical site (intra-abdominal) infection as well as any type of nosocomial infection, as defined by the Centers for Disease Control and Prevention, (ie, surgical site infections, catheter-related infections, urinary tract, pneumonia), was recorded. Hospital length of stay was a secondary endpoint. Statistical analysis included chi-square tests for coordinate variables and two-tailed unpaired t tests for continuous variables. The independence of risk factors for the development of infection was assessed by multivariate analysis of variance. Significance was determined when P <0.05. RESULTS: Three hundred patients were evaluable. There was no postoperative mortality, and no differences in overall length of hospitalization between groups. The duration of antibiotic treatment had no influence on the development of any infection (P = 0.136) or an intraabdominal infection (P = 0.336). Only colon injury was an independent predictor of the development of an intraabdominal infection (P = 0.0031). However, the overall infection incidence was affected by preoperative shock (P = 0.003), colon (P = 0.0004), central nervous system (CNS) injuries (P = 0.031), and the number of injured organs (P = 0.026). Several factors, including intraoperative shock (P = 0.021) and injuries to the colon (P = 0.0008), CNS (P = 0.0001), and chest (P = 0.0006), were independent contributors to prolongation of the hospital stay. CONCLUSIONS: Twenty-four hours of presumptive intravenous cefoxitin versus 5 days of therapy made no difference in the prevention of postoperative infection or length of hospitalization. Infection was associated with shock on admission to the emergency department, the number of intra-abdominal organs injured, colon injury specifically, and injury to the central nervous system. Intra-abdominal infection was predicted only by colon injury. Prolonged hospitalization was associated with intraoperative shock and injuries to the chest, colon, or central nervous system.

Effects of monosodium glutamate on somatic development, obesity and activity in the mouse.

Neonatal mice 1 and 5 days of age and older mice 25 days of age were injected with an increasing dose of monosodium glutamate (MSG) for a ten-day period and observed for at least 150 days. Both male and female animals in the 1- and 5-day age group treated with MSG showed large increases in weight over controls along with a shortened body length. The MSG group also showed decreases in locomotor and explatory behavior. The 25-day animals took much longer to show effects or failed to show any effects, indicating that the MSG-induced changes studied are age dependent. Possible methodological considerations accounting for conflicting reports in the MSG literature are discussed in light of the present findings.

Conditioned taste aversion is a confound in behavioral studies that report a reduction in the reinforcing effects of drugs.

Pharmacologic agents with a potential to attenuate the reinforcing properties of drugs of abuse may have an important role in the treatment of drug addiction. The reduction of drug self-administration and sweet solution intake are two common animal models employed to screen for promising therapeutic agents. When these agents are effective in suppressing the behavior maintained by drugs of abuse, the cause is usually attributed to a neuronal mechanism such as the modification of neurotransmitters that subserve reinforcement. These experiments present data for an alternate interpretation which suggest that some of these agents produce a conditioned taste aversion (CTA) that acts as a confounding variable in the screening of potential therapeutic agents. Both carbamazepine and isradipine were shown to establish a CTA at doses reported to attenuate the reinforcing properties of drugs of abuse. It is concluded that CTA represents a potential experimental confound in studies of pharmacologic agents that appear to attenuate the reinforcing properties of drugs. These results suggest that screening for a CTA is necessary in any paradigm that measures the suppression of consummatory behavior in response to pharmacologic intervention.

Developmental and behavioral effects of prenatal primidone exposure in the rat.

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-17 in doses of 0.40, and 80 mg/kg. Although these doses of PRM did not produce significant differences in litter size, birth weight, mortality, date of attainment of developmental landmarks or measures of preweaning reflex and motor development, there were a number of significant differences that developed as the animals approached and entered adulthood. When tested as adults, the 80 mg/kg male rats showed a deficit in the performance of an eight-arm radial maze task. These same animals showed a significant reduction in open field activity when tested as adults. In addition, both male and female PRM-treated animals showed reduced body weights at different periods corresponding to onset of sexual maturation during development. These findings are consistent with the larger body of literature reporting on the neurobehavioral teratology of phenobarbital, including its ability to produce lesions in the hippocampus and endocrine dysfunction resulting in reproductive deficits. These results suggest that PRM produces its adverse effects as a result of its metabolism to phenobarbital, which in turn affects the limbic system.

Somatic, behavioral, and reproductive disturbances in mice following neonatal administration of sodium L-aspartate.

Sodium L-aspartate (ASP) was administered to neonatal mice according to an increasing dose schedule from Days 2--11 after birth. Adult ASP-treated animals showed large increases in body weight over controls along with stunted body length. The ASP group also showed decreases in locomotor and exploratory behavior. Reproductive dysfunction occurred in both female and male ASP-treated animals. Among treated animals, females had fewer pregnancies and smaller litters while males showed reduced fertility. Evidence of multiple endocrine dysfunction in ASP-treated animals was reflected by decreased pituitary, thyroid, ovaries and tested weights, along with delayed onset of puberty in females. These results demonstrate that sodium L-aspartate produces a syndrome similar to that seen following the administration of monosodium L-glutamate.

Effects of prenatal diphenylhydantoin treatment on reproductive outcome, development, and behavior in rats.

Pregnant Sprague-Dawley rats were administered sodium diphenylhydantoin (DPH) by gavage on gestation days 9-18 in doses of 0, 100, or 200 mg/kg. DPH-treated dams showed a dose-related decrease in weight gain throughout the drug treatment period. Offspring had significantly lowered birth weights, along with increased mortality through the first 30 days of life. In one of the experiments specifically designed to measure pup mortality, the rates were 41.4% and 60.7% respectively, for the 100 and 200 mg/kg DPH groups. Shortly after eye opening, many of the DPH-treated animals developed chromodacryorrhea, a condition that remained throughout the experiment. Aside from lowered body weights, no differences were observed in the attainment of several standard developmental landmarks. During the neonatal period, the pups exposed in utero to 100 mg/kg DPH showed a significant increase in pivoting locomotion on postnatal days 7 and 9. As adults, the animals exposed to 200 mg/kg DPH showed significant increases in locomotor activity measures. Both DPH groups developed a dose-related and highly abnormal spontaneous circling behavior. These results confirm a small but growing body of literature that demonstrates that DPH is a behavioral teratogen.

Primidone-induced embryolethality and DRL deficits in surviving offspring.

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-20 in doses of 0 or 120 mg/kg. This dose did not produce body weight differences in the dams during the dosing period nor were there differences in the birth weights of the offspring. PRM was embryolethal with only 43% of drug-treated dams maintaining their pregnancies, whereas 100% of the pregnant controls produced offspring. An analysis of resorption sites in PRM-treated dams that did not deliver showed a nearly identical number of implantation sites (12.6) compared to the litter size of controls (12.8) that delivered pups. There were no overall differences in exploratory activity levels between PRM-treated and control animals. However, in the PRM-treated females there was an absence of the sexually dimorphic increase in activity seen in control females when compared to control males. The PRM-treated males showed an impairment in the acquisition of a DRL-20 (differential reinforcement of low rates) operant schedule over a 9-week acquisition period. There were no differences in the total response rates between the groups, suggesting that this is a specific learning deficit and not a performance deficit. The results of these experiments provide evidence that prenatal PRM exposure can be embryolethal and also impair behavior in the surviving rat offspring.

Differential effects of methylphenidate on the growth of neonatal and adolescent rats.

Methylphenidate (MPH), the drug of choice in the treatment of Attention Deficit Disorders with Hyperactivity (ADD/H), has raised concern regarding its suspected potential for reducing body stature in growing patients. In a previous study we demonstrated that neonatal rats treated with MPH (35 mg/kg, SC, twice daily) showed an acute growth impairment followed by a rapid growth-rebound phenomenon. This report confirms our earlier findings in neonatal rats and extends the investigation of the growth suppressing effects of MPH to the periadolescent period of development in rats. Specifically, neonatal groups of male and female rats treated with higher and lower doses of MPH than in the original study confirmed the growth impairment and growth rebound phenomena reported earlier. Unlike neonatal rats, rats treated during the periadolescent period of development failed to show any growth impairment. These data suggest that the growth suppressing effects of MPH are the result of an acute toxicity which is readily reversible on discontinuation of the drug. Further, it is concluded that there is a low probability of long term effects on human body stature when the minimal therapeutic dose is used in clinical practice.

Hepatic duct transection during laparoscopic cholecystectomy.

A rare anatomical variation was encountered during a laparoscopic cholecystectomy. The right hepatic duct emptied into the infundibulum of the gallbladder. This confluence then joined the left hepatic duct to form the common bile duct. The right hepatic duct was transected between the gallbladder and the common bile duct as a normal cystic duct would have been isolated and divided laparoscopicaly. This anatomic variant was recognized after further mobilization of the gallbladder from the liver bed. A laparotomy was performed to create a right hepatic duct enteric anastomosis. The case illustrates one possible pitfall that may be encountered during laparoscopic cholecystectomy.